Alzheimer’s Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment
Abstract
:1. Introduction
2. Amyloid Cascade Hypothesis
3. Tau Propagation Hypothesis
4. Biomarkers of AD
5. Biomarkers and Amyloid Cascade Hypothesis-Related Animal Models
5.1. Animal Models for Early-Onset AD
5.1.1. Tg2576
5.1.2. APP23
5.1.3. PDAPP
5.1.4. TgCRND8
5.1.5. APPPS1
5.1.6. 5XFAD
5.1.7. 3×Tg-AD
5.2. Animal Models for Late-Onset AD
5.2.1. APOE
5.2.2. TREM2
Mouse Line | Promoter | Transgene Mutation | Amyloid Plague-Deposits | Hyperphosphorylated Tau | NFTs | Reference |
---|---|---|---|---|---|---|
Tg2576 | Hamster Prion Protein | APP Swedish mutation | 11–13 months | Not detected | Not detected | [70] |
APP23 | Mouse Thy1 | APP Swedish mutation | 6 months | 6 months | Not detected | [78] |
PDAPP | Platelet-derived growth factor-β | APP Indiana mutation | 6–9 months | 14 months | Not detected | [88,89] |
TgCRND8 | Hamster Prion Protein | APP Swedish + Indiana mutations | 3–5 months | 7–12 months | Not detected | [93,94] |
APPPS1 | Mouse Thy1 (APP, PS1) | APP Swedish + PS1 L166P mutations | 2–3 months | 8 months | Not detected | [102] |
5XFAD | Mouse Thy1.2 (APP, PS1) | APP Swedish + Florida + London + PS1 M146V + L286V mutations | 1.5 months | Not detected | Not detected | [110] |
3×Tg-AD | Mouse Thy1.2 (APP, Tau) and endogenous (PS1) | APP Swedish + PS1 M146V + Tau P301L mutations | 3–6 months | 12 months | 12 months | [117] |
APP-KI | Endogenous APP | APP Swedish + Iberian + Arctic mutations | 2 months | Not detected | Not detected | [150] |
6. The Next Generation of Mouse Models and New Approaches for AD Treatment
Behavioral Tests | Test Significance | Significant Difference | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
Tg2576 | APP23 | PDAPP | TgCRND8 | APPPS1 | 5XFAD | 3xTg-AD | APP-KI | |||
Y-maze | Short-term working memory | Yes: [166] No: [125] | ― | ― | ― | ― | Yes: [112] | Yes: [125,126] | No: [156] | |
Hole board | Reference and working memory | Yes: [167] No: [167] | ― | ― | ― | ― | ― | ― | ― | |
Open-field foraging task | Working memory | ― | ― | Yes: [168] | ― | ― | ― | ― | ― | |
Object in place task | Spatial recognition memory | No: [169] | ― | ― | ― | ― | ― | ― | ― | |
Object place recognition | Short-term memory | Yes: [125] | ― | ― | ― | ― | ― | Yes: [125] | ― | |
Object-place association task | Recognition memory | ― | ― | ― | Yes: [98] | ― | ― | ― | ― | |
Spatial object location task | Recognition memory | ― | ― | ― | Yes: [98] | ― | ― | ― | ||
Spatial memory | No: [170] | |||||||||
Novel object recognition | Recognition memory | Yes: [171] No: [169] | Yes: [86] | ― | Yes: [98,100] | Yes: [108] | Yes: [113] | Yes: [122,123] | No: [156] | |
Hippocampal-dependent episodic memory | Yes: [125] | Yes: [125] | ||||||||
Social preference social novelty | Social memory | ― | ― | ― | ― | ― | ― | ― | No: [157] | |
Fear conditioning | Associative memory | No: [172] | No: [173] | ― | ― | ― | ― | |||
Contextual fear memory | Yes: [99] | Yes: [170] | ||||||||
Tone-cued fear memory | No: [170] | |||||||||
Non-hippocampal-dependent auditory fear memory | Yes: [99] | |||||||||
Fear learning | No: [155] | |||||||||
Fear conditioning context discrimination | Context discrimination learning and memory | Yes: [73] | ― | ― | ― | ― | ― | ― | ― | |
Passive avoidance | Contextual learning and memory | ― | ― | ― | ― | ― | ― | Yes: [122] | ― | |
Learning and memory | Yes: [126] | |||||||||
Eight-arm radial maze | Working memory | ― | Yes: [84] | ― | ― | ― | ― | ― | ||
Spatial learning and memory | Yes: [100] | |||||||||
Banes maze | Spatial learning and memory | ― | ― | ― | Yes: [108] | ― | ― | Yes: [155] | ||
Spatial navigation memory | Yes: [98] | |||||||||
Morris water maze | Spatial learning and memory | Yes: [124,166,171,174] No: [175] | Yes: [85] No: [86] | ― | Yes: [99] | ― | Yes: [112,113,115] | Yes: [122,124,125,126,127] | ||
Spatial recognition memory | No: [174] | |||||||||
Spatial reference memory | No: [156,157,164] | |||||||||
Spatial reversal learning | Flexibility and impulse control | ― | ― | ― | ― | ― | ― | ― | No: [155] | |
Location discrimination | Pattern separation | ― | ― | ― | ― | ― | ― | ― | Yes: [164] | |
Different object –location paired-associate learning | Paired-associative memory | ― | ― | ― | ― | ― | ― | ― | Yes: [164] | |
Visual discrimination, reversal learning | Cognitive flexibility | ― | ― | ― | ― | Yes: [109] | ― | ― | No: [164] |
7. Pharmacological Interventions in AD Animal Models
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- World Health Organization. 10 Facts on Dementia 2019. 2019. Available online: https://www.who.int/features/factfiles/dementia/en/ (accessed on 29 April 2021).
- Alzheimer’s Association. 2020 Alzheimer’s disease facts and figures. Alzheimer’s Dement. 2020. [Google Scholar] [CrossRef]
- Querfurth, H.W.; LaFerla, F.M. Alzheimer’s disease. N. Engl. J. Med. 2010, 362, 329–344. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bateman, R.J.; Xiong, C.; Benzinger, T.L.; Fagan, A.M.; Goate, A.; Fox, N.C.; Marcus, D.S.; Cairns, N.J.; Xie, X.; Blazey, T.M.; et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N. Engl. J. Med. 2012, 367, 795–804. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McKhann, G.M.; Knopman, D.S.; Chertkow, H.; Hyman, B.T.; Jack, C.R., Jr.; Kawas, C.H.; Klunk, W.E.; Koroshetz, W.J.; Manly, J.J.; Mayeux, R.; et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement. 2011, 7, 263–269. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vermunt, L.; Sikkes, S.A.M.; van den Hout, A.; Handels, R.; Bos, I.; van der Flier, W.M.; Kern, S.; Ousset, P.J.; Maruff, P.; Skoog, I.; et al. Duration of preclinical, prodromal, and dementia stages of Alzheimer’s disease in relation to age, sex, and APOE genotype. Alzheimer’s Dement. 2019, 15, 888–898. [Google Scholar] [CrossRef] [PubMed]
- Kim, D.H.; Jang, Y.S.; Jeon, W.K.; Han, J.S. Assessment of Cognitive Phenotyping in Inbred, Genetically Modified Mice, and Transgenic Mouse Models of Alzheimer’s Disease. Exp. Neurobiol. 2019, 28, 146–157. [Google Scholar] [CrossRef] [PubMed]
- Vyas, Y.; Montgomery, J.M.; Cheyne, J.E. Hippocampal Deficits in Amyloid-β-Related Rodent Models of Alzheimer’s Disease. Front. Neurosci. 2020, 14, 266. [Google Scholar] [CrossRef]
- Hardy, J.; Allsop, D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol. Sci. 1991, 12, 383–388. [Google Scholar] [CrossRef]
- Glenner, G.G.; Wong, C.W. Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 1984, 120, 885–890. [Google Scholar] [CrossRef]
- Robakis, N.K.; Ramakrishna, N.; Wolfe, G.; Wisniewski, H.M. Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc. Natl. Acad. Sci. USA 1987, 84, 4190–4194. [Google Scholar] [CrossRef] [Green Version]
- Tanzi, R.E.; Gusella, J.F.; Watkins, P.C.; Bruns, G.A.; St George-Hyslop, P.; Van Keuren, M.L.; Patterson, D.; Pagan, S.; Kurnit, D.M.; Neve, R.L. Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 1987, 235, 880–884. [Google Scholar] [CrossRef] [PubMed]
- Kang, J.; Lemaire, H.G.; Unterbeck, A.; Salbaum, J.M.; Masters, C.L.; Grzeschik, K.H.; Multhaup, G.; Beyreuther, K.; Müller-Hill, B. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 1987, 325, 733–736. [Google Scholar] [CrossRef] [PubMed]
- Haass, C.; Kaether, C.; Thinakaran, G.; Sisodia, S. Trafficking and proteolytic processing of APP. Cold Spring Harb. Perspect. Med. 2012, 2, a006270. [Google Scholar] [CrossRef] [PubMed]
- Allinson, T.M.; Parkin, E.T.; Turner, A.J.; Hooper, N.M. ADAMs family members as amyloid precursor protein alpha-secretases. J. Neurosci. Res. 2003, 74, 342–352. [Google Scholar] [CrossRef]
- Wang, J.; Dickson, D.W.; Trojanowski, J.Q.; Lee, V.M. The levels of soluble versus insoluble brain Abeta distinguish Alzheimer’s disease from normal and pathologic aging. Exp. Neurol. 1999, 158, 328–337. [Google Scholar] [CrossRef]
- Yankner, B.A.; Duffy, L.K.; Kirschner, D.A. Neurotrophic and neurotoxic effects of amyloid beta protein: Reversal by tachykinin neuropeptides. Science 1990, 250, 279–282. [Google Scholar] [CrossRef]
- Tomlinson, B.E.; Irving, D.; Blessed, G. Cell loss in the locus coeruleus in senile dementia of Alzheimer type. J. Neurol. Sci. 1981, 49, 419–428. [Google Scholar] [CrossRef]
- Whitehouse, P.J.; Price, D.L.; Clark, A.W.; Coyle, J.T.; DeLong, M.R. Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann. Neurol. 1981, 10, 122–126. [Google Scholar] [CrossRef]
- Mullan, M.; Crawford, F.; Axelman, K.; Houlden, H.; Lilius, L.; Winblad, B.; Lannfelt, L. A pathogenic mutation for probable Alzheimer’s disease in the APP gene at the N-terminus of beta-amyloid. Nat. Genet. 1992, 1, 345–347. [Google Scholar] [CrossRef]
- Di Fede, G.; Catania, M.; Morbin, M.; Rossi, G.; Suardi, S.; Mazzoleni, G.; Merlin, M.; Giovagnoli, A.R.; Prioni, S.; Erbetta, A.; et al. A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis. Science 2009, 323, 1473–1477. [Google Scholar] [CrossRef] [Green Version]
- Zhang, S.; Wang, Z.; Cai, F.; Zhang, M.; Wu, Y.; Zhang, J.; Song, W. BACE1 Cleavage Site Selection Critical for Amyloidogenesis and Alzheimer’s Pathogenesis. J. Neurosci. 2017, 37, 6915–6925. [Google Scholar] [CrossRef] [Green Version]
- Sisodia, S.S.; Koo, E.H.; Beyreuther, K.; Unterbeck, A.; Price, D.L. Evidence that beta-amyloid protein in Alzheimer’s disease is not derived by normal processing. Science 1990, 248, 492–495. [Google Scholar] [CrossRef] [PubMed]
- Ahmed, M.; Davis, J.; Aucoin, D.; Sato, T.; Ahuja, S.; Aimoto, S.; Elliott, J.I.; Van Nostrand, W.E.; Smith, S.O. Structural conversion of neurotoxic amyloid-beta(1-42) oligomers to fibrils. Nat. Struct. Mol. Biol. 2010, 17, 561–567. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mayeux, R.; Tang, M.X.; Jacobs, D.M.; Manly, J.; Bell, K.; Merchant, C.; Small, S.A.; Stern, Y.; Wisniewski, H.M.; Mehta, P.D. Plasma amyloid beta-peptide 1-42 and incipient Alzheimer’s disease. Ann. Neurol. 1999, 46, 412–416. [Google Scholar] [CrossRef]
- Frost, B.; Jacks, R.L.; Diamond, M.I. Propagation of tau misfolding from the outside to the inside of a cell. J. Biol. Chem. 2009, 284, 12845–12852. [Google Scholar] [CrossRef] [Green Version]
- Weingarten, M.D.; Lockwood, A.H.; Hwo, S.Y.; Kirschner, M.W. A protein factor essential for microtubule assembly. Proc. Natl. Acad. Sci. USA 1975, 72, 1858–1862. [Google Scholar] [CrossRef] [Green Version]
- Goedert, M.; Wischik, C.M.; Crowther, R.A.; Walker, J.E.; Klug, A. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: Identification as the microtubule-associated protein tau. Proc. Natl. Acad. Sci. USA 1988, 85, 4051–4055. [Google Scholar] [CrossRef] [Green Version]
- Cleveland, D.W.; Hwo, S.Y.; Kirschner, M.W. Purification of tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin. J. Mol. Biol. 1977, 116, 207–225. [Google Scholar] [CrossRef]
- Goedert, M.; Spillantini, M.G.; Jakes, R.; Rutherford, D.; Crowther, R.A. Multiple isoforms of human microtubule-associated protein tau: Sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron 1989, 3, 519–526. [Google Scholar] [CrossRef]
- Adams, S.J.; DeTure, M.A.; McBride, M.; Dickson, D.W.; Petrucelli, L. Three repeat isoforms of tau inhibit assembly of four repeat tau filaments. PLoS ONE 2010, 5, e10810. [Google Scholar] [CrossRef]
- Harada, A.; Oguchi, K.; Okabe, S.; Kuno, J.; Terada, S.; Ohshima, T.; Sato-Yoshitake, R.; Takei, Y.; Noda, T.; Hirokawa, N. Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature 1994, 369, 488–491. [Google Scholar] [CrossRef] [PubMed]
- Noble, W.; Hanger, D.P.; Miller, C.C.; Lovestone, S. The importance of tau phosphorylation for neurodegenerative diseases. Front. Neurol. 2013, 4, 83. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hanger, D.P.; Byers, H.L.; Wray, S.; Leung, K.Y.; Saxton, M.J.; Seereeram, A.; Reynolds, C.H.; Ward, M.A.; Anderton, B.H. Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis. J. Biol. Chem. 2007, 282, 23645–23654. [Google Scholar] [CrossRef] [Green Version]
- Tavares, I.A.; Touma, D.; Lynham, S.; Troakes, C.; Schober, M.; Causevic, M.; Garg, R.; Noble, W.; Killick, R.; Bodi, I.; et al. Prostate-derived sterile 20-like kinases (PSKs/TAOKs) phosphorylate tau protein and are activated in tangle-bearing neurons in Alzheimer disease. J. Biol. Chem. 2013, 288, 15418–15429. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tamaoka, A.; Sawamura, N.; Fukushima, T.; Shoji, S.; Matsubara, E.; Shoji, M.; Hirai, S.; Furiya, Y.; Endoh, R.; Mori, H. Amyloid beta protein 42(43) in cerebrospinal fluid of patients with Alzheimer’s disease. J. Neurol. Sci. 1997, 148, 41–45. [Google Scholar] [CrossRef]
- Skoog, I.; Davidsson, P.; Aevarsson, O.; Vanderstichele, H.; Vanmechelen, E.; Blennow, K. Cerebrospinal fluid beta-amyloid 42 is reduced before the onset of sporadic dementia: A population-based study in 85-year-olds. Dement. Geriatr. Cogn. Disord. 2003, 15, 169–176. [Google Scholar] [CrossRef]
- Vandermeeren, M.; Mercken, M.; Vanmechelen, E.; Six, J.; van de Voorde, A.; Martin, J.J.; Cras, P. Detection of tau proteins in normal and Alzheimer’s disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay. J. Neurochem. 1993, 61, 1828–1834. [Google Scholar] [CrossRef] [PubMed]
- Arai, H.; Terajima, M.; Miura, M.; Higuchi, S.; Muramatsu, T.; Machida, N.; Seiki, H.; Takase, S.; Clark, C.M.; Lee, V.M.; et al. Tau in cerebrospinal fluid: A potential diagnostic marker in Alzheimer’s disease. Ann. Neurol. 1995, 38, 649–652. [Google Scholar] [CrossRef]
- Motter, R.; Vigo-Pelfrey, C.; Kholodenko, D.; Barbour, R.; Johnson-Wood, K.; Galasko, D.; Chang, L.; Miller, B.; Clark, C.; Green, R.; et al. Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer’s disease. Ann. Neurol. 1995, 38, 643–648. [Google Scholar] [CrossRef]
- Shoji, M.; Matsubara, E.; Kanai, M.; Watanabe, M.; Nakamura, T.; Tomidokoro, Y.; Shizuka, M.; Wakabayashi, K.; Igeta, Y.; Ikeda, Y.; et al. Combination assay of CSF tau, A beta 1-40 and A beta 1-42(43) as a biochemical marker of Alzheimer’s disease. J. Neurol. Sci. 1998, 158, 134–140. [Google Scholar] [CrossRef]
- Fukumoto, H.; Tokuda, T.; Kasai, T.; Ishigami, N.; Hidaka, H.; Kondo, M.; Allsop, D.; Nakagawa, M. High-molecular-weight beta-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients. FASEB J. 2010, 24, 2716–2726. [Google Scholar] [CrossRef] [PubMed]
- Murakami, K.; Tokuda, M.; Suzuki, T.; Irie, Y.; Hanaki, M.; Izuo, N.; Monobe, Y.; Akagi, K.; Ishii, R.; Tatebe, H.; et al. Monoclonal antibody with conformational specificity for a toxic conformer of amyloid β42 and its application toward the Alzheimer’s disease diagnosis. Sci. Rep. 2016, 6, 29038. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klunk, W.E.; Engler, H.; Nordberg, A.; Wang, Y.; Blomqvist, G.; Holt, D.P.; Bergström, M.; Savitcheva, I.; Huang, G.F.; Estrada, S.; et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann. Neurol. 2004, 55, 306–319. [Google Scholar] [CrossRef]
- Villemagne, V.L.; Burnham, S.; Bourgeat, P.; Brown, B.; Ellis, K.A.; Salvado, O.; Szoeke, C.; Macaulay, S.L.; Martins, R.; Maruff, P.; et al. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: A prospective cohort study. Lancet Neurol. 2013, 12, 357–367. [Google Scholar] [CrossRef]
- Yang, L.; Rieves, D.; Ganley, C. Brain amyloid imaging--FDA approval of florbetapir F18 injection. N. Engl. J. Med. 2012, 367, 885–887. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lister-James, J.; Pontecorvo, M.J.; Clark, C.; Joshi, A.D.; Mintun, M.A.; Zhang, W.; Lim, N.; Zhuang, Z.; Golding, G.; Choi, S.R.; et al. Florbetapir f-18: A histopathologically validated Beta-amyloid positron emission tomography imaging agent. Semin. Nucl. Med. 2011, 41, 300–304. [Google Scholar] [CrossRef]
- Harada, R.; Okamura, N.; Furumoto, S.; Furukawa, K.; Ishiki, A.; Tomita, N.; Tago, T.; Hiraoka, K.; Watanuki, S.; Shidahara, M.; et al. 18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease. J. Nucl. Med. 2016, 57, 208–214. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Johnson, K.A.; Schultz, A.; Betensky, R.A.; Becker, J.A.; Sepulcre, J.; Rentz, D.; Mormino, E.; Chhatwal, J.; Amariglio, R.; Papp, K.; et al. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann. Neurol. 2016, 79, 110–119. [Google Scholar] [CrossRef] [Green Version]
- Cagnin, A.; Brooks, D.J.; Kennedy, A.M.; Gunn, R.N.; Myers, R.; Turkheimer, F.E.; Jones, T.; Banati, R.B. In-vivo measurement of activated microglia in dementia. Lancet 2001, 358, 461–467. [Google Scholar] [CrossRef]
- Yasuno, F.; Ota, M.; Kosaka, J.; Ito, H.; Higuchi, M.; Doronbekov, T.K.; Nozaki, S.; Fujimura, Y.; Koeda, M.; Asada, T.; et al. Increased binding of peripheral benzodiazepine receptor in Alzheimer’s disease measured by positron emission tomography with [11C]DAA1106. Biol. Psychiatry 2008, 64, 835–841. [Google Scholar] [CrossRef]
- Rembach, A.; Faux, N.G.; Watt, A.D.; Pertile, K.K.; Rumble, R.L.; Trounson, B.O.; Fowler, C.J.; Roberts, B.R.; Perez, K.A.; Li, Q.X.; et al. Changes in plasma amyloid beta in a longitudinal study of aging and Alzheimer’s disease. Alzheimer’s Dement. 2014, 10, 53–61. [Google Scholar] [CrossRef] [PubMed]
- Wood, H. Alzheimer disease: Biomarkers of AD risk - the end of the road for plasma amyloid-β? Nat. Rev. Neurol. 2016, 12, 613. [Google Scholar] [CrossRef] [PubMed]
- Lövheim, H.; Elgh, F.; Johansson, A.; Zetterberg, H.; Blennow, K.; Hallmans, G.; Eriksson, S. Plasma concentrations of free amyloid β cannot predict the development of Alzheimer’s disease. Alzheimer’s Dement. 2017, 13, 778–782. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kaneko, N.; Nakamura, A.; Washimi, Y.; Kato, T.; Sakurai, T.; Arahata, Y.; Bundo, M.; Takeda, A.; Niida, S.; Ito, K.; et al. Novel plasma biomarker surrogating cerebral amyloid deposition. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 2014, 90, 353–364. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ovod, V.; Ramsey, K.N.; Mawuenyega, K.G.; Bollinger, J.G.; Hicks, T.; Schneider, T.; Sullivan, M.; Paumier, K.; Holtzman, D.M.; Morris, J.C.; et al. Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimer’s Dement. 2017, 13, 841–849. [Google Scholar] [CrossRef] [PubMed]
- Nakamura, A.; Kaneko, N.; Villemagne, V.L.; Kato, T.; Doecke, J.; Doré, V.; Fowler, C.; Li, Q.X.; Martins, R.; Rowe, C.; et al. High performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature 2018, 554, 249–254. [Google Scholar] [CrossRef]
- Fandos, N.; Pérez-Grijalba, V.; Pesini, P.; Olmos, S.; Bossa, M.; Villemagne, V.L.; Doecke, J.; Fowler, C.; Masters, C.L.; Sarasa, M. Plasma amyloid β 42/40 ratios as biomarkers for amyloid β cerebral deposition in cognitively normal individuals. Alzheimers Dement (Amst). 2017, 8, 179–187. [Google Scholar] [CrossRef]
- Nabers, A.; Perna, L.; Lange, J.; Mons, U.; Schartner, J.; Güldenhaupt, J.; Saum, K.U.; Janelidze, S.; Holleczek, B.; Rujescu, D.; et al. Amyloid blood biomarker detects Alzheimer’s disease. EMBO Mol. Med. 2018, 10. [Google Scholar] [CrossRef]
- Tatebe, H.; Kasai, T.; Ohmichi, T.; Kishi, Y.; Kakeya, T.; Waragai, M.; Kondo, M.; Allsop, D.; Tokuda, T. Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: Pilot case-control studies including patients with Alzheimer’s disease and down syndrome. Mol. Neurodegener. 2017, 12, 63. [Google Scholar] [CrossRef] [Green Version]
- Janelidze, S.; Mattsson, N.; Palmqvist, S.; Smith, R.; Beach, T.G.; Serrano, G.E.; Chai, X.; Proctor, N.K.; Eichenlaub, U.; Zetterberg, H.; et al. Plasma P-tau181 in Alzheimer’s disease: Relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia. Nat. Med. 2020, 26, 379–386. [Google Scholar] [CrossRef]
- Thijssen, E.H.; La Joie, R.; Wolf, A.; Strom, A.; Wang, P.; Iaccarino, L.; Bourakova, V.; Cobigo, Y.; Heuer, H.; Spina, S.; et al. Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration. Nat. Med. 2020, 26, 387–397. [Google Scholar] [CrossRef] [PubMed]
- Bettcher, B.M.; Johnson, S.C.; Fitch, R.; Casaletto, K.B.; Heffernan, K.S.; Asthana, S.; Zetterberg, H.; Blennow, K.; Carlsson, C.M.; Neuhaus, J.; et al. Cerebrospinal Fluid and Plasma Levels of Inflammation Differentially Relate to CNS Markers of Alzheimer’s Disease Pathology and Neuronal Damage. J. Alzheimers Dis. 2018, 62, 385–397. [Google Scholar] [CrossRef] [PubMed]
- Mattsson, N.; Andreasson, U.; Zetterberg, H.; Blennow, K. Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease. JAMA Neurol. 2017, 74, 557–566. [Google Scholar] [CrossRef] [PubMed]
- Shigemizu, D.; Akiyama, S.; Asanomi, Y.; Boroevich, K.A.; Sharma, A.; Tsunoda, T.; Matsukuma, K.; Ichikawa, M.; Sudo, H.; Takizawa, S.; et al. Risk prediction models for dementia constructed by supervised principal component analysis using miRNA expression data. Commun Biol. 2019, 2, 77. [Google Scholar] [CrossRef] [Green Version]
- Wennberg, A.M.V.; Hagen, C.E.; Machulda, M.M.; Hollman, J.H.; Roberts, R.O.; Knopman, D.S.; Petersen, R.C.; Mielke, M.M. The association between peripheral total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 and functional and cognitive outcomes in the Mayo Clinic Study of Aging. Neurobiol. Aging 2018, 66, 68–74. [Google Scholar] [CrossRef]
- Liu, S.; Suzuki, H.; Ito, H.; Korenaga, T.; Akatsu, H.; Meno, K.; Uchida, K. Serum levels of proteins involved in amyloid-β clearance are related to cognitive decline and neuroimaging changes in mild cognitive impairment. Alzheimers Dement (Amst). 2019, 11, 85–97. [Google Scholar] [CrossRef]
- Cruts, M.; van Duijn, C.M.; Backhovens, H.; Van den Broeck, M.; Wehnert, A.; Serneels, S.; Sherrington, R.; Hutton, M.; Hardy, J.; St George-Hyslop, P.H.; et al. Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. Hum. Mol. Genet. 1998, 7, 43–51. [Google Scholar] [CrossRef] [PubMed]
- Cuyvers, E.; Sleegers, K. Genetic variations underlying Alzheimer’s disease: Evidence from genome-wide association studies and beyond. Lancet Neurol. 2016, 15, 857–868. [Google Scholar] [CrossRef]
- Hsiao, K.; Chapman, P.; Nilsen, S.; Eckman, C.; Harigaya, Y.; Younkin, S.; Yang, F.; Cole, G. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 1996, 274, 99–102. [Google Scholar] [CrossRef]
- Benzing, W.C.; Wujek, J.R.; Ward, E.K.; Shaffer, D.; Ashe, K.H.; Younkin, S.G.; Brunden, K.R. Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice. Neurobiol. Aging 1999, 20, 581–589. [Google Scholar] [CrossRef]
- Corcoran, K.A.; Lu, Y.; Turner, R.S.; Maren, S. Overexpression of hAPPswe impairs rewarded alternation and contextual fear conditioning in a transgenic mouse model of Alzheimer’s disease. Learn. Mem. 2002, 9, 243–252. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cortez, I.; Hernandez, C.M.; Dineley, K.T. Enhancement of select cognitive domains with rosiglitazone implicates dorsal hippocampus circuitry sensitive to PPARγ agonism in an Alzheimer’s mouse model. Brain Behav. 2021, 11, e01973. [Google Scholar] [CrossRef] [PubMed]
- Barnes, P.; Good, M. Impaired Pavlovian cued fear conditioning in Tg2576 mice expressing a human mutant amyloid precursor protein gene. Behav. Brain Res. 2005, 157, 107–117. [Google Scholar] [CrossRef] [PubMed]
- Scopa, C.; Marrocco, F.; Latina, V.; Ruggeri, F.; Corvaglia, V.; La Regina, F.; Ammassari-Teule, M.; Middei, S.; Amadoro, G.; Meli, G.; et al. Impaired adult neurogenesis is an early event in Alzheimer’s disease neurodegeneration, mediated by intracellular Aβ oligomers. Cell Death Differ. 2020, 27, 934–948. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Braak, H.; Braak, E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991, 82, 239–259. [Google Scholar] [CrossRef] [PubMed]
- Yang, F.; Uéda, K.; Chen, P.; Ashe, K.H.; Cole, G.M. Plaque-associated alpha-synuclein (NACP) pathology in aged transgenic mice expressing amyloid precursor protein. Brain Res. 2000, 853, 381–383. [Google Scholar] [CrossRef]
- Sturchler-Pierrat, C.; Abramowski, D.; Duke, M.; Wiederhold, K.H.; Mistl, C.; Rothacher, S.; Ledermann, B.; Bürki, K.; Frey, P.; Paganetti, P.A.; et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc. Natl. Acad. Sci. USA 1997, 94, 13287–13292. [Google Scholar] [CrossRef] [Green Version]
- Calhoun, M.E.; Wiederhold, K.H.; Abramowski, D.; Phinney, A.L.; Probst, A.; Sturchler-Pierrat, C.; Staufenbiel, M.; Sommer, B.; Jucker, M. Neuron loss in APP transgenic mice. Nature 1998, 395, 755–756. [Google Scholar] [CrossRef]
- Bondolfi, L.; Calhoun, M.; Ermini, F.; Kuhn, H.G.; Wiederhold, K.H.; Walker, L.; Staufenbiel, M.; Jucker, M. Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. J. Neurosci. 2002, 22, 515–522. [Google Scholar] [CrossRef] [Green Version]
- Calhoun, M.E.; Burgermeister, P.; Phinney, A.L.; Stalder, M.; Tolnay, M.; Wiederhold, K.H.; Abramowski, D.; Sturchler-Pierrat, C.; Sommer, B.; Staufenbiel, M.; et al. Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid. Proc. Natl. Acad. Sci. USA 1999, 96, 14088–14093. [Google Scholar] [CrossRef] [Green Version]
- Kelly, P.H.; Bondolfi, L.; Hunziker, D.; Schlecht, H.P.; Carver, K.; Maguire, E.; Abramowski, D.; Wiederhold, K.H.; Sturchler-Pierrat, C.; Jucker, M.; et al. Progressive age-related impairment of cognitive behavior in APP23 transgenic mice. Neurobiol. Aging 2003, 24, 365–378. [Google Scholar] [CrossRef]
- Van Dam, D.; D’Hooge, R.; Staufenbiel, M.; Van Ginneken, C.; Van Meir, F.; De Deyn, P.P. Age-dependent cognitive decline in the APP23 model precedes amyloid deposition. Eur. J. Neurosci. 2003, 17, 388–396. [Google Scholar] [CrossRef]
- Liu, X.; Yamashita, T.; Shang, J.; Shi, X.; Morihara, R.; Huang, Y.; Sato, K.; Takemoto, M.; Hishikawa, N.; Ohta, Y.; et al. Clinical and Pathological Benefit of Twendee X in Alzheimer’s Disease Transgenic Mice with Chronic Cerebral Hypoperfusion. J. Stroke Cerebrovasc. Dis. 2019, 28, 1993–2002. [Google Scholar] [CrossRef] [PubMed]
- Van Erum, J.; Van Dam, D.; Sheorajpanday, R.; De Deyn, P.P. Sleep architecture changes in the APP23 mouse model manifest at onset of cognitive deficits. Behav. Brain Res. 2019, 373, 112089. [Google Scholar] [CrossRef] [PubMed]
- Sorgdrager, F.; van Der Ley, C.P.; van Faassen, M.; Calus, E.; Nollen, E.A.; Kema, I.P.; van Dam, D.; De Deyn, P.P. The Effect of Tryptophan 2,3-Dioxygenase Inhibition on Kynurenine Metabolism and Cognitive Function in the APP23 Mouse Model of Alzheimer’s Disease. Int. J. Tryptophan Res. 2020, 13, 1178646920972657. [Google Scholar] [CrossRef] [PubMed]
- Chartier-Harlin, M.C.; Crawford, F.; Houlden, H.; Warren, A.; Hughes, D.; Fidani, L.; Goate, A.; Rossor, M.; Roques, P.; Hardy, J.; et al. Early-onset Alzheimer’s disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature 1991, 353, 844–846. [Google Scholar] [CrossRef] [PubMed]
- Games, D.; Adams, D.; Alessandrini, R.; Barbour, R.; Berthelette, P.; Blackwell, C.; Carr, T.; Clemens, J.; Donaldson, T.; Gillespie, F.; et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 1995, 373, 523–527. [Google Scholar] [CrossRef]
- Masliah, E.; Sisk, A.; Mallory, M.; Games, D. Neurofibrillary pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. J. Neuropathol. Exp. Neurol. 2001, 60, 357–368. [Google Scholar] [CrossRef] [Green Version]
- Dodart, J.C.; Meziane, H.; Mathis, C.; Bales, K.R.; Paul, S.M.; Ungerer, A. Behavioral disturbances in transgenic mice overexpressing the V717F beta-amyloid precursor protein. Behav. Neurosci. 1999, 113, 982–990. [Google Scholar] [CrossRef]
- Chen, G.; Chen, K.S.; Knox, J.; Inglis, J.; Bernard, A.; Martin, S.J.; Justice, A.; McConlogue, L.; Games, D.; Freedman, S.B.; et al. A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer’s disease. Nature 2000, 408, 975–979. [Google Scholar] [CrossRef]
- Hartman, R.E.; Izumi, Y.; Bales, K.R.; Paul, S.M.; Wozniak, D.F.; Holtzman, D.M. Treatment with an amyloid-beta antibody ameliorates plaque load, learning deficits, and hippocampal long-term potentiation in a mouse model of Alzheimer’s disease. J. Neurosci. 2005, 25, 6213–6220. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chishti, M.A.; Yang, D.S.; Janus, C.; Phinney, A.L.; Horne, P.; Pearson, J.; Strome, R.; Zuker, N.; Loukides, J.; French, J.; et al. Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J. Biol. Chem. 2001, 276, 21562–21570. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bellucci, A.; Rosi, M.C.; Grossi, C.; Fiorentini, A.; Luccarini, I.; Casamenti, F. Abnormal processing of tau in the brain of aged TgCRND8 mice. Neurobiol. Dis. 2007, 27, 328–338. [Google Scholar] [CrossRef] [PubMed]
- Brautigam, H.; Steele, J.W.; Westaway, D.; Fraser, P.E.; St George-Hyslop, P.H.; Gandy, S.; Hof, P.R.; Dickstein, D.L. The isotropic fractionator provides evidence for differential loss of hippocampal neurons in two mouse models of Alzheimer’s disease. Mol. Neurodegener. 2012, 7, 58. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Janus, C.; Pearson, J.; McLaurin, J.; Mathews, P.M.; Jiang, Y.; Schmidt, S.D.; Chishti, M.A.; Horne, P.; Heslin, D.; French, J.; et al. A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer’s disease. Nature 2000, 408, 979–982. [Google Scholar] [CrossRef] [PubMed]
- Ambrée, O.; Touma, C.; Görtz, N.; Keyvani, K.; Paulus, W.; Palme, R.; Sachser, N. Activity changes and marked stereotypic behavior precede Abeta pathology in TgCRND8 Alzheimer mice. Neurobiol. Aging 2006, 27, 955–964. [Google Scholar] [CrossRef]
- Hamm, V.; Héraud, C.; Bott, J.B.; Herbeaux, K.; Strittmatter, C.; Mathis, C.; Goutagny, R. Differential contribution of APP metabolites to early cognitive deficits in a TgCRND8 mouse model of Alzheimer’s disease. Sci. Adv. 2017, 3, e1601068. [Google Scholar] [CrossRef] [Green Version]
- Xia, F.; Yiu, A.; Stone, S.S.D.; Oh, S.; Lozano, A.M.; Josselyn, S.A.; Frankland, P.W. Entorhinal Cortical Deep Brain Stimulation Rescues Memory Deficits in Both Young and Old Mice Genetically Engineered to Model Alzheimer’s Disease. Neuropsychopharmacology 2017, 42, 2493–2503. [Google Scholar] [CrossRef] [Green Version]
- Xian, Y.F.; Qu, C.; Liu, Y.; Ip, S.P.; Yuan, Q.J.; Yang, W.; Lin, Z.X. Magnolol Ameliorates Behavioral Impairments and Neuropathology in a Transgenic Mouse Model of Alzheimer’s Disease. Oxid. Med. Cell. Longev. 2020, 2020, 5920476. [Google Scholar] [CrossRef]
- Woodhouse, A.; Vickers, J.C.; Adlard, P.A.; Dickson, T.C. Dystrophic neurites in TgCRND8 and Tg2576 mice mimic human pathological brain aging. Neurobiol. Aging 2009, 30, 864–874. [Google Scholar] [CrossRef] [PubMed]
- Radde, R.; Bolmont, T.; Kaeser, S.A.; Coomaraswamy, J.; Lindau, D.; Stoltze, L.; Calhoun, M.E.; Jäggi, F.; Wolburg, H.; Gengler, S.; et al. Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Rep. 2006, 7, 940–946. [Google Scholar] [CrossRef] [Green Version]
- Rupp, N.J.; Wegenast-Braun, B.M.; Radde, R.; Calhoun, M.E.; Jucker, M. Early onset amyloid lesions lead to severe neuritic abnormalities and local, but not global neuron loss in APPPS1 transgenic mice. Neurobiol. Aging 2011, 32, 2324.e2321–2326. [Google Scholar] [CrossRef] [PubMed]
- Bittner, T.; Burgold, S.; Dorostkar, M.M.; Fuhrmann, M.; Wegenast-Braun, B.M.; Schmidt, B.; Kretzschmar, H.; Herms, J. Amyloid plaque formation precedes dendritic spine loss. Acta Neuropathol. 2012, 124, 797–807. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Serneels, L.; Van Biervliet, J.; Craessaerts, K.; Dejaegere, T.; Horré, K.; Van Houtvin, T.; Esselmann, H.; Paul, S.; Schäfer, M.K.; Berezovska, O.; et al. gamma-Secretase heterogeneity in the Aph1 subunit: Relevance for Alzheimer’s disease. Science 2009, 324, 639–642. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Montarolo, F.; Parolisi, R.; Hoxha, E.; Boda, E.; Tempia, F. Early enriched environment exposure protects spatial memory and accelerates amyloid plaque formation in APP(Swe)/PS1(L166P) mice. PLoS ONE 2013, 8, e69381. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cifuentes, D.; Poittevin, M.; Dere, E.; Broquères-You, D.; Bonnin, P.; Benessiano, J.; Pocard, M.; Mariani, J.; Kubis, N.; Merkulova-Rainon, T.; et al. Hypertension accelerates the progression of Alzheimer-like pathology in a mouse model of the disease. Hypertension 2015, 65, 218–224. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wagner, L.K.; Gilling, K.E.; Schormann, E.; Kloetzel, P.M.; Heppner, F.L.; Krüger, E.; Prokop, S. Immunoproteasome deficiency alters microglial cytokine response and improves cognitive deficits in Alzheimer’s disease-like APPPS1 mice. Acta Neuropathol. Commun. 2017, 5, 52. [Google Scholar] [CrossRef]
- Van den Broeck, L.; Hansquine, P.; Callaerts-Vegh, Z.; D’Hooge, R. Impaired Reversal Learning in APPPS1-21 Mice in the Touchscreen Visual Discrimination Task. Front. Behav. Neurosci. 2019, 13, 92. [Google Scholar] [CrossRef] [Green Version]
- Oakley, H.; Cole, S.L.; Logan, S.; Maus, E.; Shao, P.; Craft, J.; Guillozet-Bongaarts, A.; Ohno, M.; Disterhoft, J.; Van Eldik, L.; et al. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: Potential factors in amyloid plaque formation. J. Neurosci. 2006, 26, 10129–10140. [Google Scholar] [CrossRef]
- Eimer, W.A.; Vassar, R. Neuron loss in the 5XFAD mouse model of Alzheimer’s disease correlates with intraneuronal Aβ42 accumulation and Caspase-3 activation. Mol. Neurodegener. 2013, 8, 2. [Google Scholar] [CrossRef] [Green Version]
- Chen, W.; Wang, M.; Zhu, M.; Xiong, W.; Qin, X.; Zhu, X. 14,15-Epoxyeicosatrienoic Acid Alleviates Pathology in a Mouse Model of Alzheimer’s Disease. J. Neurosci. 2020, 40, 8188–8203. [Google Scholar] [CrossRef] [PubMed]
- Ramasamy, V.S.; Samidurai, M.; Park, H.J.; Wang, M.; Park, R.Y.; Yu, S.Y.; Kang, H.K.; Hong, S.; Choi, W.S.; Lee, Y.Y.; et al. Avenanthramide-C Restores Impaired Plasticity and Cognition in Alzheimer’s Disease Model Mice. Mol. Neurobiol. 2020, 57, 315–330. [Google Scholar] [CrossRef] [PubMed]
- Ohno, M.; Chang, L.; Tseng, W.; Oakley, H.; Citron, M.; Klein, W.L.; Vassar, R.; Disterhoft, J.F. Temporal memory deficits in Alzheimer’s mouse models: Rescue by genetic deletion of BACE1. Eur. J. Neurosci. 2006, 23, 251–260. [Google Scholar] [CrossRef] [PubMed]
- Oh, S.B.; Kim, M.S.; Park, S.; Son, H.; Kim, S.Y.; Kim, M.S.; Jo, D.G.; Tak, E.; Lee, J.Y. Clusterin contributes to early stage of Alzheimer’s disease pathogenesis. Brain Pathol. 2019, 29, 217–231. [Google Scholar] [CrossRef] [PubMed]
- Zhong, L.; Xu, Y.; Zhuo, R.; Wang, T.; Wang, K.; Huang, R.; Wang, D.; Gao, Y.; Zhu, Y.; Sheng, X.; et al. Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer’s disease model. Nat. Commun. 2019, 10, 1365. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oddo, S.; Caccamo, A.; Shepherd, J.D.; Murphy, M.P.; Golde, T.E.; Kayed, R.; Metherate, R.; Mattson, M.P.; Akbari, Y.; LaFerla, F.M. Triple-transgenic model of Alzheimer’s disease with plaques and tangles: Intracellular Abeta and synaptic dysfunction. Neuron 2003, 39, 409–421. [Google Scholar] [CrossRef] [Green Version]
- Billings, L.M.; Oddo, S.; Green, K.N.; McGaugh, J.L.; LaFerla, F.M. Intraneuronal Abeta causes the onset of early Alzheimer’s disease-related cognitive deficits in transgenic mice. Neuron 2005, 45, 675–688. [Google Scholar] [CrossRef] [Green Version]
- Manaye, K.F.; Mouton, P.R.; Xu, G.; Drew, A.; Lei, D.L.; Sharma, Y.; Rebeck, G.W.; Turner, S. Age-related loss of noradrenergic neurons in the brains of triple transgenic mice. Age (Dordr). 2013, 35, 139–147. [Google Scholar] [CrossRef] [Green Version]
- Janelsins, M.C.; Mastrangelo, M.A.; Park, K.M.; Sudol, K.L.; Narrow, W.C.; Oddo, S.; LaFerla, F.M.; Callahan, L.M.; Federoff, H.J.; Bowers, W.J. Chronic neuron-specific tumor necrosis factor-alpha expression enhances the local inflammatory environment ultimately leading to neuronal death in 3xTg-AD mice. Am. J. Pathol. 2008, 173, 1768–1782. [Google Scholar] [CrossRef] [Green Version]
- Kastyak-Ibrahim, M.Z.; Di Curzio, D.L.; Buist, R.; Herrera, S.L.; Albensi, B.C.; Del Bigio, M.R.; Martin, M. Neurofibrillary tangles and plaques are not accompanied by white matter pathology in aged triple transgenic-Alzheimer disease mice. Magn. Reson. Imaging 2013, 31, 1515–1521. [Google Scholar] [CrossRef]
- Scuderi, C.; Bronzuoli, M.R.; Facchinetti, R.; Pace, L.; Ferraro, L.; Broad, K.D.; Serviddio, G.; Bellanti, F.; Palombelli, G.; Carpinelli, G.; et al. Ultramicronized palmitoylethanolamide rescues learning and memory impairments in a triple transgenic mouse model of Alzheimer’s disease by exerting anti-inflammatory and neuroprotective effects. Transl Psychiatry 2018, 8, 32. [Google Scholar] [CrossRef] [PubMed]
- Barone, E.; Tramutola, A.; Triani, F.; Calcagnini, S.; Di Domenico, F.; Ripoli, C.; Gaetani, S.; Grassi, C.; Butterfield, D.A.; Cassano, T.; et al. Biliverdin Reductase-A Mediates the Beneficial Effects of Intranasal Insulin in Alzheimer Disease. Mol. Neurobiol. 2019, 56, 2922–2943. [Google Scholar] [CrossRef]
- Escrig, A.; Canal, C.; Sanchis, P.; Fernández-Gayol, O.; Montilla, A.; Comes, G.; Molinero, A.; Giralt, M.; Giménez-Llort, L.; Becker-Pauly, C.; et al. IL-6 trans-signaling in the brain influences the behavioral and physio-pathological phenotype of the Tg2576 and 3xTgAD mouse models of Alzheimer’s disease. Brain. Behav. Immun. 2019, 82, 145–159. [Google Scholar] [CrossRef] [PubMed]
- Corsetti, V.; Borreca, A.; Latina, V.; Giacovazzo, G.; Pignataro, A.; Krashia, P.; Natale, F.; Cocco, S.; Rinaudo, M.; Malerba, F.; et al. Passive immunotherapy for N-truncated tau ameliorates the cognitive deficits in two mouse Alzheimer’s disease models. Brain Commun. 2020, 2, fcaa039. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shen, Y.; Hua, L.; Yeh, C.K.; Shen, L.; Ying, M.; Zhang, Z.; Liu, G.; Li, S.; Chen, S.; Chen, X.; et al. Ultrasound with microbubbles improves memory, ameliorates pathology and modulates hippocampal proteomic changes in a triple transgenic mouse model of Alzheimer’s disease. Theranostics 2020, 10, 11794–11819. [Google Scholar] [CrossRef]
- Correia, S.C.; Machado, N.J.; Alves, M.G.; Oliveira, P.F.; Moreira, P.I. Intermittent Hypoxic Conditioning Rescues Cognition and Mitochondrial Bioenergetic Profile in the Triple Transgenic Mouse Model of Alzheimer’s Disease. Int. J. Mol. Sci. 2021, 22, 461. [Google Scholar] [CrossRef]
- Zannis, V.I.; Kardassis, D.; Zanni, E.E. Genetic mutations affecting human lipoproteins, their receptors, and their enzymes. Adv. Hum. Genet. 1993, 21, 145–319. [Google Scholar] [CrossRef]
- Liu, C.C.; Liu, C.C.; Kanekiyo, T.; Xu, H.; Bu, G. Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy. Nat. Rev. Neurol. 2013, 9, 106–118. [Google Scholar] [CrossRef] [Green Version]
- Hoe, H.S.; Lee, K.J.; Carney, R.S.; Lee, J.; Markova, A.; Lee, J.Y.; Howell, B.W.; Hyman, B.T.; Pak, D.T.; Bu, G.; et al. Interaction of reelin with amyloid precursor protein promotes neurite outgrowth. J. Neurosci. 2009, 29, 7459–7473. [Google Scholar] [CrossRef]
- Bales, K.R.; Liu, F.; Wu, S.; Lin, S.; Koger, D.; DeLong, C.; Hansen, J.C.; Sullivan, P.M.; Paul, S.M. Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice. J. Neurosci. 2009, 29, 6771–6779. [Google Scholar] [CrossRef]
- Bour, A.; Grootendorst, J.; Vogel, E.; Kelche, C.; Dodart, J.C.; Bales, K.; Moreau, P.H.; Sullivan, P.M.; Mathis, C. Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks. Behav. Brain Res. 2008, 193, 174–182. [Google Scholar] [CrossRef] [PubMed]
- Dumanis, S.B.; Tesoriero, J.A.; Babus, L.W.; Nguyen, M.T.; Trotter, J.H.; Ladu, M.J.; Weeber, E.J.; Turner, R.S.; Xu, B.; Rebeck, G.W.; et al. ApoE4 decreases spine density and dendritic complexity in cortical neurons in vivo. J. Neurosci. 2009, 29, 15317–15322. [Google Scholar] [CrossRef] [PubMed]
- Sullivan, P.M.; Han, B.; Liu, F.; Mace, B.E.; Ervin, J.F.; Wu, S.; Koger, D.; Paul, S.; Bales, K.R. Reduced levels of human apoE4 protein in an animal model of cognitive impairment. Neurobiol. Aging 2011, 32, 791–801. [Google Scholar] [CrossRef]
- Bales, K.R.; Verina, T.; Dodel, R.C.; Du, Y.; Altstiel, L.; Bender, M.; Hyslop, P.; Johnstone, E.M.; Little, S.P.; Cummins, D.J.; et al. Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition. Nat. Genet. 1997, 17, 263–264. [Google Scholar] [CrossRef] [PubMed]
- Fryer, J.D.; Simmons, K.; Parsadanian, M.; Bales, K.R.; Paul, S.M.; Sullivan, P.M.; Holtzman, D.M. Human apolipoprotein E4 alters the amyloid-beta 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model. J. Neurosci. 2005, 25, 2803–2810. [Google Scholar] [CrossRef] [Green Version]
- Liao, F.; Zhang, T.J.; Jiang, H.; Lefton, K.B.; Robinson, G.O.; Vassar, R.; Sullivan, P.M.; Holtzman, D.M. Murine versus human apolipoprotein E4: Differential facilitation of and co-localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models. Acta Neuropathol. Commun. 2015, 3, 70. [Google Scholar] [CrossRef] [Green Version]
- Allcock, R.J.; Barrow, A.D.; Forbes, S.; Beck, S.; Trowsdale, J. The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44. Eur. J. Immunol. 2003, 33, 567–577. [Google Scholar] [CrossRef]
- Chertoff, M.; Shrivastava, K.; Gonzalez, B.; Acarin, L.; Giménez-Llort, L. Differential modulation of TREM2 protein during postnatal brain development in mice. PLoS ONE 2013, 8, e72083. [Google Scholar] [CrossRef] [Green Version]
- Bhattacharjee, S.; Zhao, Y.; Dua, P.; Rogaev, E.I.; Lukiw, W.J. microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular Degeneration. PLoS ONE 2016, 11, e0150211. [Google Scholar] [CrossRef] [PubMed]
- Zhou, S.L.; Tan, C.C.; Hou, X.H.; Cao, X.P.; Tan, L.; Yu, J.T. TREM2 Variants and Neurodegenerative Diseases: A Systematic Review and Meta-Analysis. J. Alzheimers Dis. 2019, 68, 1171–1184. [Google Scholar] [CrossRef]
- Kober, D.L.; Alexander-Brett, J.M.; Karch, C.M.; Cruchaga, C.; Colonna, M.; Holtzman, M.J.; Brett, T.J. Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms. Elife 2016, 5. [Google Scholar] [CrossRef]
- Kawabori, M.; Kacimi, R.; Kauppinen, T.; Calosing, C.; Kim, J.Y.; Hsieh, C.L.; Nakamura, M.C.; Yenari, M.A. Triggering receptor expressed on myeloid cells 2 (TREM2) deficiency attenuates phagocytic activities of microglia and exacerbates ischemic damage in experimental stroke. J. Neurosci. 2015, 35, 3384–3396. [Google Scholar] [CrossRef] [PubMed]
- Lue, L.F.; Schmitz, C.T.; Serrano, G.; Sue, L.I.; Beach, T.G.; Walker, D.G. TREM2 Protein Expression Changes Correlate with Alzheimer’s Disease Neurodegenerative Pathologies in Post-Mortem Temporal Cortices. Brain Pathol. 2015, 25, 469–480. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Perez, S.E.; Nadeem, M.; He, B.; Miguel, J.C.; Malek-Ahmadi, M.H.; Chen, K.; Mufson, E.J. Neocortical and hippocampal TREM2 protein levels during the progression of Alzheimer’s disease. Neurobiol. Aging 2017, 54, 133–143. [Google Scholar] [CrossRef] [PubMed]
- Jay, T.R.; Miller, C.M.; Cheng, P.J.; Graham, L.C.; Bemiller, S.; Broihier, M.L.; Xu, G.; Margevicius, D.; Karlo, J.C.; Sousa, G.L.; et al. TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models. J. Exp. Med. 2015, 212, 287–295. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Cella, M.; Mallinson, K.; Ulrich, J.D.; Young, K.L.; Robinette, M.L.; Gilfillan, S.; Krishnan, G.M.; Sudhakar, S.; Zinselmeyer, B.H.; et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell 2015, 160, 1061–1071. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.; Ulland, T.K.; Ulrich, J.D.; Song, W.; Tzaferis, J.A.; Hole, J.T.; Yuan, P.; Mahan, T.E.; Shi, Y.; Gilfillan, S.; et al. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J. Exp. Med. 2016, 213, 667–675. [Google Scholar] [CrossRef] [Green Version]
- Jay, T.R.; Hirsch, A.M.; Broihier, M.L.; Miller, C.M.; Neilson, L.E.; Ransohoff, R.M.; Lamb, B.T.; Landreth, G.E. Disease Progression-Dependent Effects of TREM2 Deficiency in a Mouse Model of Alzheimer’s Disease. J. Neurosci. 2017, 37, 637–647. [Google Scholar] [CrossRef]
- Saito, T.; Matsuba, Y.; Mihira, N.; Takano, J.; Nilsson, P.; Itohara, S.; Iwata, N.; Saido, T.C. Single App knock-in mouse models of Alzheimer’s disease. Nat. Neurosci. 2014, 17, 661–663. [Google Scholar] [CrossRef]
- Pardossi-Piquard, R.; Checler, F. The physiology of the β-amyloid precursor protein intracellular domain AICD. J. Neurochem. 2012, 120 Suppl 1, 109–124. [Google Scholar] [CrossRef]
- Mitani, Y.; Yarimizu, J.; Saita, K.; Uchino, H.; Akashiba, H.; Shitaka, Y.; Ni, K.; Matsuoka, N. Differential effects between γ-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. J. Neurosci. 2012, 32, 2037–2050. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sasaguri, H.; Nilsson, P.; Hashimoto, S.; Nagata, K.; Saito, T.; De Strooper, B.; Hardy, J.; Vassar, R.; Winblad, B.; Saido, T.C. APP mouse models for Alzheimer’s disease preclinical studies. EMBO J. 2017, 36, 2473–2487. [Google Scholar] [CrossRef] [PubMed]
- Masuda, A.; Kobayashi, Y.; Kogo, N.; Saito, T.; Saido, T.C.; Itohara, S. Cognitive deficits in single App knock-in mouse models. Neurobiol. Learn. Mem. 2016, 135, 73–82. [Google Scholar] [CrossRef] [Green Version]
- Sakakibara, Y.; Sekiya, M.; Saito, T.; Saido, T.C.; Iijima, K.M. Cognitive and emotional alterations in App knock-in mouse models of Aβ amyloidosis. BMC Neurosci. 2018, 19, 46. [Google Scholar] [CrossRef] [PubMed]
- Whyte, L.S.; Hemsley, K.M.; Lau, A.A.; Hassiotis, S.; Saito, T.; Saido, T.C.; Hopwood, J.J.; Sargeant, T.J. Reduction in open field activity in the absence of memory deficits in the App(NL-G-F) knock-in mouse model of Alzheimer’s disease. Behav. Brain Res. 2018, 336, 177–181. [Google Scholar] [CrossRef] [PubMed]
- Latif-Hernandez, A.; Shah, D.; Craessaerts, K.; Saido, T.; Saito, T.; De Strooper, B.; Van der Linden, A.; D’Hooge, R. Subtle behavioral changes and increased prefrontal-hippocampal network synchronicity in APP(NL-G-F) mice before prominent plaque deposition. Behav. Brain Res. 2019, 364, 431–441. [Google Scholar] [CrossRef] [Green Version]
- De Roeck, E.E.; Engelborghs, S.; Dierckx, E. Next Generation Brain Health Depends on Early Alzheimer Disease Diagnosis: From a Timely Diagnosis to Future Population Screening. J. Am. Med. Dir. Assoc. 2016, 17, 452–453. [Google Scholar] [CrossRef] [PubMed]
- Farlow, M.; Anand, R.; Messina, J., Jr.; Hartman, R.; Veach, J. A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer’s disease. Eur. Neurol. 2000, 44, 236–241. [Google Scholar] [CrossRef] [PubMed]
- Doraiswamy, P.M.; Krishnan, K.R.; Anand, R.; Sohn, H.; Danyluk, J.; Hartman, R.D.; Veach, J. Long-term effects of rivastigmine in moderately severe Alzheimer’s disease: Does early initiation of therapy offer sustained benefits? Prog. Neuropsychopharmacol. Biol. Psychiatry 2002, 26, 705–712. [Google Scholar] [CrossRef]
- Romberg, C.; Mattson, M.P.; Mughal, M.R.; Bussey, T.J.; Saksida, L.M. Impaired attention in the 3xTgAD mouse model of Alzheimer’s disease: Rescue by donepezil (Aricept). J. Neurosci. 2011, 31, 3500–3507. [Google Scholar] [CrossRef] [Green Version]
- Bussey, T.J.; Holmes, A.; Lyon, L.; Mar, A.C.; McAllister, K.A.; Nithianantharajah, J.; Oomen, C.A.; Saksida, L.M. New translational assays for preclinical modelling of cognition in schizophrenia: The touchscreen testing method for mice and rats. Neuropharmacology 2012, 62, 1191–1203. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Romberg, C.; Bussey, T.J.; Saksida, L.M. Paying more attention to attention: Towards more comprehensive cognitive translation using mouse models of Alzheimer’s disease. Brain Res. Bull. 2013, 92, 49–55. [Google Scholar] [CrossRef] [PubMed]
- Saifullah, M.A.B.; Komine, O.; Dong, Y.; Fukumoto, K.; Sobue, A.; Endo, F.; Saito, T.; Saido, T.C.; Yamanaka, K.; Mizoguchi, H. Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer’s disease. Mol. Brain 2020, 13, 147. [Google Scholar] [CrossRef] [PubMed]
- Sobue, A.; Komine, O.; Hara, Y.; Endo, F.; Mizoguchi, H.; Watanabe, S.; Murayama, S.; Saito, T.; Saido, T.C.; Sahara, N.; et al. Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer’s disease. Acta Neuropathol. Commun. 2021, 9, 1. [Google Scholar] [CrossRef]
- Kim, K.Y.; Suh, Y.H.; Chang, K.A. Therapeutic Effects of Human Amniotic Epithelial Stem Cells in a Transgenic Mouse Model of Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 2658. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schmid, S.; Rammes, G.; Blobner, M.; Kellermann, K.; Bratke, S.; Fendl, D.; Kaichuan, Z.; Schneider, G.; Jungwirth, B. Cognitive decline in Tg2576 mice shows sex-specific differences and correlates with cerebral amyloid-beta. Behav. Brain Res. 2019, 359, 408–417. [Google Scholar] [CrossRef]
- Evans, C.; Hvoslef-Eide, M.; Thomas, R.; Kidd, E.; Good, M.A. A rapidly acquired foraging-based working memory task, sensitive to hippocampal lesions, reveals age-dependent and age-independent behavioural changes in a mouse model of amyloid pathology. Neurobiol. Learn. Mem. 2018, 149, 46–57. [Google Scholar] [CrossRef] [PubMed]
- Lim, S.L.; Tran, D.N.; Kieu, Z.; Chen, C.; Villanueva, E.; Ghiaar, S.; Gallup, V.; Zumkehr, J.; Cribbs, D.H.; Rodriguez-Ortiz, C.J.; et al. Genetic Ablation of Hematopoietic Cell Kinase Accelerates Alzheimer’s Disease-Like Neuropathology in Tg2576 Mice. Mol. Neurobiol. 2020, 57, 2447–2460. [Google Scholar] [CrossRef]
- Tanaka, T.; Hirai, S.; Hosokawa, M.; Saito, T.; Sakuma, H.; Saido, T.; Hasegawa, M.; Okado, H. Early-life stress induces the development of Alzheimer’s disease pathology via angiopathy. Exp. Neurol. 2021, 337, 113552. [Google Scholar] [CrossRef]
- Chun, Y.S.; Zhang, L.; Li, H.; Park, Y.; Chung, S.; Yang, H.O. 7-Deoxy-trans-dihydronarciclasine Reduces β-Amyloid and Ameliorates Memory Impairment in a Transgenic Model of Alzheimer’s Disease. Mol. Neurobiol. 2018, 55, 8953–8964. [Google Scholar] [CrossRef]
- Pignataro, A.; Meli, G.; Pagano, R.; Fontebasso, V.; Battistella, R.; Conforto, G.; Ammassari-Teule, M.; Middei, S. Activity-Induced Amyloid-β Oligomers Drive Compensatory Synaptic Rearrangements in Brain Circuits Controlling Memory of Presymptomatic Alzheimer’s Disease Mice. Biol. Psychiatry 2019, 86, 185–195. [Google Scholar] [CrossRef] [PubMed]
- Vilella, A.; Belletti, D.; Sauer, A.K.; Hagmeyer, S.; Sarowar, T.; Masoni, M.; Stasiak, N.; Mulvihill, J.J.E.; Ruozi, B.; Forni, F.; et al. Reduced plaque size and inflammation in the APP23 mouse model for Alzheimer’s disease after chronic application of polymeric nanoparticles for CNS targeted zinc delivery. J. Trace Elem. Med. Biol. 2018, 49, 210–221. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Liu, D.; Huang, H.Z.; Wang, Z.H.; Hou, T.Y.; Yang, X.; Pang, P.; Wei, N.; Zhou, Y.F.; Dupras, M.J.; et al. A Novel MicroRNA-124/PTPN1 Signal Pathway Mediates Synaptic and Memory Deficits in Alzheimer’s Disease. Biol. Psychiatry 2018, 83, 395–405. [Google Scholar] [CrossRef] [PubMed]
- Elhaik Goldman, S.; Goez, D.; Last, D.; Naor, S.; Liraz Zaltsman, S.; Sharvit-Ginon, I.; Atrakchi-Baranes, D.; Shemesh, C.; Twitto-Greenberg, R.; Tsach, S.; et al. High-fat diet protects the blood-brain barrier in an Alzheimer’s disease mouse model. Aging Cell 2018, 17, e12818. [Google Scholar] [CrossRef]
- Dong, H.; Csernansky, C.A.; Martin, M.V.; Bertchume, A.; Vallera, D.; Csernansky, J.G. Acetylcholinesterase inhibitors ameliorate behavioral deficits in the Tg2576 mouse model of Alzheimer’s disease. Psychopharmacology (Berl.) 2005, 181, 145–152. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Unger, C.; Svedberg, M.M.; Yu, W.F.; Hedberg, M.M.; Nordberg, A. Effect of subchronic treatment of memantine, galantamine, and nicotine in the brain of Tg2576 (APPswe) transgenic mice. J. Pharmacol. Exp. Ther. 2006, 317, 30–36. [Google Scholar] [CrossRef]
- Dong, H.; Yuede, C.M.; Coughlan, C.; Lewis, B.; Csernansky, J.G. Effects of memantine on neuronal structure and conditioned fear in the Tg2576 mouse model of Alzheimer’s disease. Neuropsychopharmacology 2008, 33, 3226–3236. [Google Scholar] [CrossRef]
- Dong, H.; Yuede, C.M.; Coughlan, C.A.; Murphy, K.M.; Csernansky, J.G. Effects of donepezil on amyloid-beta and synapse density in the Tg2576 mouse model of Alzheimer’s disease. Brain Res. 2009, 1303, 169–178. [Google Scholar] [CrossRef] [Green Version]
- Van Dam, D.; Abramowski, D.; Staufenbiel, M.; De Deyn, P.P. Symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model. Psychopharmacology (Berlin) 2005, 180, 177–190. [Google Scholar] [CrossRef]
- Rogers, S.L.; Doody, R.S.; Mohs, R.C.; Friedhoff, L.T. Donepezil improves cognition and global function in Alzheimer disease: A 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Arch. Intern. Med. 1998, 158, 1021–1031. [Google Scholar] [CrossRef]
- Winblad, B.; Cummings, J.; Andreasen, N.; Grossberg, G.; Onofrj, M.; Sadowsky, C.; Zechner, S.; Nagel, J.; Lane, R. A six-month double-blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer’s disease--rivastigmine patch versus capsule. Int. J. Geriatr. Psychiatry 2007, 22, 456–467. [Google Scholar] [CrossRef] [PubMed]
- Kavanagh, S.; Van Baelen, B.; Schäuble, B. Long-term effects of galantamine on cognitive function in Alzheimer’s disease: A large-scale international retrospective study. J. Alzheimers Dis. 2011, 27, 521–530. [Google Scholar] [CrossRef] [PubMed]
- Wilkinson, D.; Fox, N.C.; Barkhof, F.; Phul, R.; Lemming, O.; Scheltens, P. Memantine and brain atrophy in Alzheimer’s disease: A 1-year randomized controlled trial. J. Alzheimers Dis. 2012, 29, 459–469. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lim, G.P.; Yang, F.; Chu, T.; Chen, P.; Beech, W.; Teter, B.; Tran, T.; Ubeda, O.; Ashe, K.H.; Frautschy, S.A.; et al. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer’s disease. J. Neurosci. 2000, 20, 5709–5714. [Google Scholar] [CrossRef]
- Kotilinek, L.A.; Westerman, M.A.; Wang, Q.; Panizzon, K.; Lim, G.P.; Simonyi, A.; Lesne, S.; Falinska, A.; Younkin, L.H.; Younkin, S.G.; et al. Cyclooxygenase-2 inhibition improves amyloid-beta-mediated suppression of memory and synaptic plasticity. Brain 2008, 131, 651–664. [Google Scholar] [CrossRef]
- McKee, A.C.; Carreras, I.; Hossain, L.; Ryu, H.; Klein, W.L.; Oddo, S.; LaFerla, F.M.; Jenkins, B.G.; Kowall, N.W.; Dedeoglu, A. Ibuprofen reduces Abeta, hyperphosphorylated tau and memory deficits in Alzheimer mice. Brain Res. 2008, 1207, 225–236. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hillmann, A.; Hahn, S.; Schilling, S.; Hoffmann, T.; Demuth, H.U.; Bulic, B.; Schneider-Axmann, T.; Bayer, T.A.; Weggen, S.; Wirths, O. No improvement after chronic ibuprofen treatment in the 5XFAD mouse model of Alzheimer’s disease. Neurobiol. Aging 2012, 33, 833.e839–850. [Google Scholar] [CrossRef]
- Babiloni, C.; Frisoni, G.B.; Del Percio, C.; Zanetti, O.; Bonomini, C.; Cassetta, E.; Pasqualetti, P.; Miniussi, C.; De Rosas, M.; Valenzano, A.; et al. Ibuprofen treatment modifies cortical sources of EEG rhythms in mild Alzheimer’s disease. Clin. Neurophysiol. 2009, 120, 709–718. [Google Scholar] [CrossRef] [Green Version]
- Pasqualetti, P.; Bonomini, C.; Dal Forno, G.; Paulon, L.; Sinforiani, E.; Marra, C.; Zanetti, O.; Rossini, P.M. A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer’s disease. Aging Clin. Exp. Res. 2009, 21, 102–110. [Google Scholar] [CrossRef]
- Nenov, M.N.; Laezza, F.; Haidacher, S.J.; Zhao, Y.; Sadygov, R.G.; Starkey, J.M.; Spratt, H.; Luxon, B.A.; Dineley, K.T.; Denner, L. Cognitive enhancing treatment with a PPARγ agonist normalizes dentate granule cell presynaptic function in Tg2576 APP mice. J. Neurosci. 2014, 34, 1028–1036. [Google Scholar] [CrossRef] [Green Version]
- O’Reilly, J.A.; Lynch, M. Rosiglitazone improves spatial memory and decreases insoluble Aβ(1-42) in APP/PS1 mice. J. Neuroimmune Pharmacol. 2012, 7, 140–144. [Google Scholar] [CrossRef]
- Searcy, J.L.; Phelps, J.T.; Pancani, T.; Kadish, I.; Popovic, J.; Anderson, K.L.; Beckett, T.L.; Murphy, M.P.; Chen, K.C.; Blalock, E.M.; et al. Long-term pioglitazone treatment improves learning and attenuates pathological markers in a mouse model of Alzheimer’s disease. J. Alzheimers Dis. 2012, 30, 943–961. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gold, M.; Alderton, C.; Zvartau-Hind, M.; Egginton, S.; Saunders, A.M.; Irizarry, M.; Craft, S.; Landreth, G.; Linnamägi, U.; Sawchak, S. Rosiglitazone monotherapy in mild-to-moderate Alzheimer’s disease: Results from a randomized, double-blind, placebo-controlled phase III study. Dement. Geriatr. Cogn. Disord. 2010, 30, 131–146. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tzimopoulou, S.; Cunningham, V.J.; Nichols, T.E.; Searle, G.; Bird, N.P.; Mistry, P.; Dixon, I.J.; Hallett, W.A.; Whitcher, B.; Brown, A.P.; et al. A multi-center randomized proof-of-concept clinical trial applying [¹⁸F]FDG-PET for evaluation of metabolic therapy with rosiglitazone XR in mild to moderate Alzheimer’s disease. J. Alzheimers Dis. 2010, 22, 1241–1256. [Google Scholar] [CrossRef] [PubMed]
- Harrington, C.; Sawchak, S.; Chiang, C.; Davies, J.; Donovan, C.; Saunders, A.M.; Irizarry, M.; Jeter, B.; Zvartau-Hind, M.; van Dyck, C.H.; et al. Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer’s disease: Two phase 3 studies. Curr. Alzheimer Res. 2011, 8, 592–606. [Google Scholar] [CrossRef] [PubMed]
- Miller, B.W.; Willett, K.C.; Desilets, A.R. Rosiglitazone and pioglitazone for the treatment of Alzheimer’s disease. Ann. Pharmacother. 2011, 45, 1416–1424. [Google Scholar] [CrossRef] [PubMed]
- Li, G.; Mayer, C.L.; Morelli, D.; Millard, S.P.; Raskind, W.H.; Petrie, E.C.; Cherrier, M.; Fagan, A.M.; Raskind, M.A.; Peskind, E.R. Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults. Neurology 2017, 89, 1251–1255. [Google Scholar] [CrossRef]
- Umeda, T.; Ono, K.; Sakai, A.; Yamashita, M.; Mizuguchi, M.; Klein, W.L.; Yamada, M.; Mori, H.; Tomiyama, T. Rifampicin is a candidate preventive medicine against amyloid-β and tau oligomers. Brain 2016, 139, 1568–1586. [Google Scholar] [CrossRef] [Green Version]
- Fukumoto, H.; Takahashi, H.; Tarui, N.; Matsui, J.; Tomita, T.; Hirode, M.; Sagayama, M.; Maeda, R.; Kawamoto, M.; Hirai, K.; et al. A noncompetitive BACE1 inhibitor TAK-070 ameliorates Abeta pathology and behavioral deficits in a mouse model of Alzheimer’s disease. J. Neurosci. 2010, 30, 11157–11166. [Google Scholar] [CrossRef]
- May, P.C.; Dean, R.A.; Lowe, S.L.; Martenyi, F.; Sheehan, S.M.; Boggs, L.N.; Monk, S.A.; Mathes, B.M.; Mergott, D.J.; Watson, B.M.; et al. Robust central reduction of amyloid-β in humans with an orally available, non-peptidic β-secretase inhibitor. J. Neurosci. 2011, 31, 16507–16516. [Google Scholar] [CrossRef] [Green Version]
- Elvang, A.B.; Volbracht, C.; Pedersen, L.; Jensen, K.G.; Karlsson, J.J.; Larsen, S.A.; Mørk, A.; Stensbøl, T.B.; Bastlund, J.F. Differential effects of gamma-secretase and BACE1 inhibition on brain Abeta levels in vitro and in vivo. J. Neurochem. 2009, 110, 1377–1387. [Google Scholar] [CrossRef] [PubMed]
- Extance, A. Alzheimer’s failure raises questions about disease-modifying strategies. Nat. Rev. Drug Discov. 2010, 9, 749–751. [Google Scholar] [CrossRef] [PubMed]
- Doody, R.S.; Raman, R.; Farlow, M.; Iwatsubo, T.; Vellas, B.; Joffe, S.; Kieburtz, K.; He, F.; Sun, X.; Thomas, R.G.; et al. A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. N. Engl. J. Med. 2013, 369, 341–350. [Google Scholar] [CrossRef] [PubMed]
- Egan, M.F.; Kost, J.; Tariot, P.N.; Aisen, P.S.; Cummings, J.L.; Vellas, B.; Sur, C.; Mukai, Y.; Voss, T.; Furtek, C.; et al. Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer’s Disease. N. Engl. J. Med. 2018, 378, 1691–1703. [Google Scholar] [CrossRef] [PubMed]
- Schenk, D.; Barbour, R.; Dunn, W.; Gordon, G.; Grajeda, H.; Guido, T.; Hu, K.; Huang, J.; Johnson-Wood, K.; Khan, K.; et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999, 400, 173–177. [Google Scholar] [CrossRef] [PubMed]
- Morgan, D.; Diamond, D.M.; Gottschall, P.E.; Ugen, K.E.; Dickey, C.; Hardy, J.; Duff, K.; Jantzen, P.; DiCarlo, G.; Wilcock, D.; et al. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer’s disease. Nature 2000, 408, 982–985. [Google Scholar] [CrossRef]
- Kotilinek, L.A.; Bacskai, B.; Westerman, M.; Kawarabayashi, T.; Younkin, L.; Hyman, B.T.; Younkin, S.; Ashe, K.H. Reversible memory loss in a mouse transgenic model of Alzheimer’s disease. J. Neurosci. 2002, 22, 6331–6335. [Google Scholar] [CrossRef]
- Wilcock, D.M.; DiCarlo, G.; Henderson, D.; Jackson, J.; Clarke, K.; Ugen, K.E.; Gordon, M.N.; Morgan, D. Intracranially administered anti-Abeta antibodies reduce beta-amyloid deposition by mechanisms both independent of and associated with microglial activation. J. Neurosci. 2003, 23, 3745–3751. [Google Scholar] [CrossRef]
- Bard, F.; Cannon, C.; Barbour, R.; Burke, R.L.; Games, D.; Grajeda, H.; Guido, T.; Hu, K.; Huang, J.; Johnson-Wood, K.; et al. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat. Med. 2000, 6, 916–919. [Google Scholar] [CrossRef] [Green Version]
- Dodart, J.C.; Bales, K.R.; Gannon, K.S.; Greene, S.J.; DeMattos, R.B.; Mathis, C.; DeLong, C.A.; Wu, S.; Wu, X.; Holtzman, D.M.; et al. Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer’s disease model. Nat. Neurosci. 2002, 5, 452–457. [Google Scholar] [CrossRef] [PubMed]
- Gilman, S.; Koller, M.; Black, R.S.; Jenkins, L.; Griffith, S.G.; Fox, N.C.; Eisner, L.; Kirby, L.; Rovira, M.B.; Forette, F.; et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005, 64, 1553–1562. [Google Scholar] [CrossRef]
- Vellas, B.; Black, R.; Thal, L.J.; Fox, N.C.; Daniels, M.; McLennan, G.; Tompkins, C.; Leibman, C.; Pomfret, M.; Grundman, M. Long-term follow-up of patients immunized with AN1792: Reduced functional decline in antibody responders. Curr. Alzheimer Res. 2009, 6, 144–151. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Delnomdedieu, M.; Duvvuri, S.; Li, D.J.; Atassi, N.; Lu, M.; Brashear, H.R.; Liu, E.; Ness, S.; Kupiec, J.W. First-In-Human safety and long-term exposure data for AAB-003 (PF-05236812) and biomarkers after intravenous infusions of escalating doses in patients with mild to moderate Alzheimer’s disease. Alzheimers Res. Ther. 2016, 8, 12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ostrowitzki, S.; Lasser, R.A.; Dorflinger, E.; Scheltens, P.; Barkhof, F.; Nikolcheva, T.; Ashford, E.; Retout, S.; Hofmann, C.; Delmar, P.; et al. A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease. Alzheimers Res. Ther. 2017, 9, 95. [Google Scholar] [CrossRef]
- Honig, L.S.; Vellas, B.; Woodward, M.; Boada, M.; Bullock, R.; Borrie, M.; Hager, K.; Andreasen, N.; Scarpini, E.; Liu-Seifert, H.; et al. Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease. N. Engl. J. Med. 2018, 378, 321–330. [Google Scholar] [CrossRef] [PubMed]
- Tolar, M.; Abushakra, S.; Hey, J.A.; Porsteinsson, A.; Sabbagh, M. Aducanumab, gantenerumab, BAN2401, and ALZ-801-the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval. Alzheimers Res. Ther. 2020, 12, 95. [Google Scholar] [CrossRef]
- Vandenberghe, R.; Riviere, M.E.; Caputo, A.; Sovago, J.; Maguire, R.P.; Farlow, M.; Marotta, G.; Sanchez-Valle, R.; Scheltens, P.; Ryan, J.M.; et al. Active Aβ immunotherapy CAD106 in Alzheimer’s disease: A phase 2b study. Alzheimers Dement (N Y). 2017, 3, 10–22. [Google Scholar] [CrossRef]
- van Dyck, C.H. Anti-Amyloid-β Monoclonal Antibodies for Alzheimer’s Disease: Pitfalls and Promise. Biol. Psychiatry 2018, 83, 311–319. [Google Scholar] [CrossRef] [Green Version]
- Sevigny, J.; Chiao, P.; Bussière, T.; Weinreb, P.H.; Williams, L.; Maier, M.; Dunstan, R.; Salloway, S.; Chen, T.; Ling, Y.; et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature 2016, 537, 50–56. [Google Scholar] [CrossRef]
- Theunis, C.; Crespo-Biel, N.; Gafner, V.; Pihlgren, M.; López-Deber, M.P.; Reis, P.; Hickman, D.T.; Adolfsson, O.; Chuard, N.; Ndao, D.M.; et al. Efficacy and safety of a liposome-based vaccine against protein Tau, assessed in tau.P301L mice that model tauopathy. PLoS ONE 2013, 8, e72301. [Google Scholar] [CrossRef] [Green Version]
- Novak, P.; Schmidt, R.; Kontsekova, E.; Kovacech, B.; Smolek, T.; Katina, S.; Fialova, L.; Prcina, M.; Parrak, V.; Dal-Bianco, P.; et al. FUNDAMANT: An interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer’s disease. Alzheimers Res. Ther. 2018, 10, 108. [Google Scholar] [CrossRef] [PubMed] [Green Version]
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Nakai, T.; Yamada, K.; Mizoguchi, H. Alzheimer’s Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment. Int. J. Mol. Sci. 2021, 22, 5549. https://doi.org/10.3390/ijms22115549
Nakai T, Yamada K, Mizoguchi H. Alzheimer’s Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment. International Journal of Molecular Sciences. 2021; 22(11):5549. https://doi.org/10.3390/ijms22115549
Chicago/Turabian StyleNakai, Tsuyoshi, Kiyofumi Yamada, and Hiroyuki Mizoguchi. 2021. "Alzheimer’s Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment" International Journal of Molecular Sciences 22, no. 11: 5549. https://doi.org/10.3390/ijms22115549