A Novel Rare PSEN2 Val226Ala in PSEN2 in a Korean Patient with Atypical Alzheimer’s Disease, and the Importance of PSEN2 5th Transmembrane Domain (TM5) in AD Pathogenesis
Abstract
:1. Introduction
2. Results
2.1. Case Presentation
2.2. PSEN2 Val226Ala Mutation
2.3. Structure Prediction on Mutations in PSEN2 TM5
3. Discussion
Mutation | Disease | AOO | Family History | Biomarker/Imaging | Functional Data | Reference: |
---|---|---|---|---|---|---|
Leu225Pro | EOAD | NA | NA | NA | NA | [17] |
Val226Ala | AD with hallucinations | 59 | NA | Positive in both Amyloid PET and plasma OAβ | NA | Current case |
Gln228Leu | MCI, insomnia, personality changes | 60s | Probable positive | NA | NA | [31] |
Tyr231Cys | FTD: behavioral/language impairment | 52 | Probable positive | Diffuse cortical and subcortical atrophy | NA | [18] |
Ile235Phe | EOAD | NA | Probable positive (segregation not proven) | NA | Increased Ab42/40 ratio | [32,33] |
Ala237Val | AD | 87 | Probable negative | AD-type neuropathology | NA | [34] |
Leu238Phe | EOAD | 49–57 | Positive | NA | Increased Ab42/40 ratio | [36,37,38] |
EOAD | NA | Negative | NA | [35] | ||
Leu238Pro | Progressive aphasia | 54 | Negative | Atrophy in parietal cortex | NA | [39] |
AD | Over 60 | NA | NA | [40] | ||
Met239Val | AD, cognitive decline, seizure, depression | 45–83 | Positive | Diffuse cerebral atrophy with plaques and NFTs | Elevated Ab42/40 ratio | [13] |
EOAD | 47–67 | Probable positive | NA | [48] | ||
EOAD | 53 | Probable negative | NA | [49] | ||
EOAD, personality changes, seizures | 50s | Probable positive | NA | [44] | ||
Met239Thr | EOAD, visual impairment | 59 | Negative | parietal and occipital cortex atrophy, amyloid deposition | NA | [14] |
EOAD | 47 | Probable positive | CSF positive for AD markers | [46] | ||
Met239Ile | AD, motor and language impairments | 44–58 | Probable positive | Senile plaques, NFTs in brain | Elevated Ab42/40 ratio, impaired Ca+ homeostasis | [46] |
Memory impairment, language and personality changes | 45–50 | Probable positive | NA | [41] | ||
AD, depression, visuospatial impairment | 42–64 | Probable positive | bilateral parietal hypometabolism | [42] |
4. Materials and Methods
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- De Strooper, B.; Beullens, M.; Contreras, B.; Levesque, L.; Craessaerts, K.; Cordell, B.; Moechars, D.; Bollen, M.; Fraser, P.; George-Hyslop, P.S.; et al. Phosphorylation, subcellular localization, and membrane orientation of the Alzheimer’s disease-associated presenilins. J. Biol. Chem. 1997, 272, 3590–3598. [Google Scholar] [CrossRef] [PubMed]
- Rademakers, R.; Cruts, M.; Van Broeckhoven, C. Genetics of early-onset Alzheimer dementia. Sci. World J. 2003, 3, 497–519. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Cai, Y.; An, S.S.; Kim, S. Mutations in presenilin 2 and its implications in Alzheimer’s disease and other dementia-associated disorders. Clin. Interv. Aging 2015, 10, 1163–1172. [Google Scholar] [CrossRef] [PubMed]
- Hajjhussein, H.; Gardner, L.A.; Fujii, N.; Anderson, N.M.; Bahouth, S.W. The hydrophobic amino acid cluster at the cytoplasmic end of transmembrane helix III modulates the coupling of the β(1)-adrenergic receptor to G(s). J. Recept. Signal Transduct. 2013, 33, 79–88. [Google Scholar] [CrossRef] [PubMed]
- De Marothy, M.T.; Elofsson, A. Marginally hydrophobic transmembrane α-helices shaping membrane protein folding. Protein Sci. 2015, 24, 1057–1074. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Heyden, M.; Freites, J.A.; Ulmschneider, M.B.; White, S.H.; Tobias, D.J. Assembly and Stability of α-Helical Membrane Proteins. Soft Matter. 2012, 8, 7742–7752. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Finckh, U.; Alberici, A.; Antoniazzi, M.; Benussi, L.; Fedi, V.; Giannini, C.; Gal, A.; Nitsch, R.M.; Binetti, G. Variable expression of familial Alzheimer disease associated with presenilin 2 mutation M239I. Neurology 2000, 54, 2006–2008. [Google Scholar] [CrossRef] [PubMed]
- Dong, L.; Liu, C.; Sha, L.; Mao, C.; Li, J.; Huang, X.; Wang, J.; Chu, S.; Peng, B.; Cui, L.; et al. PSEN2 Mutation Spectrum and Novel Functionally Validated Mutations in Alzheimer’s Disease: Data from PUMCH Dementia Cohort. J. Alzheimers Dis. 2022, 87, 1549–1556. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Perrone, F.; Bjerke, M.; Hens, E.; Sieben, A.; Timmers, M.; De Roeck, A.; Vandenberghe, R.; Sleegers, K.; Martin, J.J.; De Deyn, P.P.; et al. Amyloid-β1-43 cerebrospinal fluid levels and the interpretation of APP, PSEN1 and PSEN2 mutations. Alzheimers Res. Ther. 2020, 12, 108. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Ertekin-Taner, N.; Younkin, L.H.; Yager, D.M.; Parfitt, F.; Baker, M.C.; Asthana, S.; Hutton, M.L.; Younkin, S.G.; Graff-Radford, N.R. Plasma amyloid beta protein is elevated in late-onset Alzheimer disease families. Neurology 2008, 70, 596–606. [Google Scholar] [CrossRef] [PubMed]
- Levy-Lahad, E.; Wasco, W.; Poorkaj, P.; Romano, D.M.; Oshima, J.; Pettingell, W.H.; Yu, C.E.; Jondro, P.D.; Schmidt, S.D.; Wang, K.; et al. Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 1995, 269, 973–977. [Google Scholar] [CrossRef] [PubMed]
- Niu, F.; Yu, S.; Zhang, Z.; Yi, X.; Ye, L.; Tang, W.; Qiu, C.; Wen, H.; Sun, Y.; Gao, J.; et al. Novel mutation in the PSEN2 gene (N141Y) associated with early-onset autosomal dominant Alzheimer’s disease in a Chinese Han family. Neurobiol. Aging 2014, 35, 2420-e1, Erratum in: Neurobiol. Aging 2014, 35, 2885. [Google Scholar] [CrossRef] [PubMed]
- Rogaev, E.I.; Sherrington, R.; Rogaeva, E.A.; Levesque, G.; Ikeda, M.; Liang, Y.; Chi, H.; Lin, C.; Holman, K.; Tsuda, T.; et al. Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature 1995, 376, 775–778. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Xiao, X.; Wang, J.; Shen, L.; Jiao, B. Early-onset familial Alzheimer’s disease in a family with mutation of presenilin 2 gene. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021, 46, 189–194, (In English, Chinese). [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Cruchaga, C.; Haller, G.; Chakraverty, S.; Mayo, K.; Vallania, F.L.; Mitra, R.D.; Faber, K.; Williamson, J.; Bird, T.; Diaz-Arrastia, R.; et al. Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer’s disease families. PLoS ONE 2012, 7, e31039, Erratum in PLoS ONE 2012, 7. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Kauwe, J.S.; Jacquart, S.; Chakraverty, S.; Wang, J.; Mayo, K.; Fagan, A.M.; Holtzman, D.M.; Morris, J.C.; Goate, A.M. Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer’s disease presenilin 1 mutation. Ann. Neurol. 2007, 61, 446–453. [Google Scholar] [CrossRef] [PubMed]
- Koriath, C.; Kenny, J.; Adamson, G.; Druyeh, R.; Taylor, W.; Beck, J.; Quinn, L.; Mok, T.H.; Dimitriadis, A.; Norsworthy, P.; et al. Predictors for a dementia gene mutation based on gene-panel next-generation sequencing of a large dementia referral series. Mol. Psychiatry 2020, 25, 3399–3412. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Marcon, G.; Di Fede, G.; Giaccone, G.; Rossi, G.; Giovagnoli, A.R.; Maccagnano, E.; Tagliavini, F. A novel Italian presenilin 2 gene mutation with prevalent behavioral phenotype. J. Alzheimers Dis. 2009, 16, 3–11. [Google Scholar] [CrossRef] [PubMed]
- Meeus, B.; Verstraeten, A.; Crosiers, D.; Engelborghs, S.; Van den Broeck, M.; Mattheijssens, M.; Peeters, K.; Corsmit, E.; Elinck, E.; Pickut, B.; et al. DLB and PDD: A role for mutations in dementia and Parkinson disease genes? Neurobiol. Aging 2012, 33, 629.e5–629.e18. [Google Scholar] [CrossRef] [PubMed]
- Li, D.; Parks, S.B.; Kushner, J.D.; Nauman, D.; Burgess, D.; Ludwigsen, S.; Partain, J.; Nixon, R.R.; Allen, C.N.; Irwin, R.P.; et al. Mutations of presenilin genes in dilated cardiomyopathy and heart failure. Am. J. Hum. Genet. 2006, 79, 1030–1039. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- To, M.D.; Gokgoz, N.; Doyle, T.G.; Donoviel, D.B.; Knight, J.A.; Hyslop, P.S.; Bernstein, A.; Andrulis, I.L. Functional characterization of novel presenilin-2 variants identified in human breast cancers. Oncogene 2006, 25, 3557–3564. [Google Scholar] [CrossRef] [PubMed]
- Fedeli, C.; Filadi, R.; Rossi, A.; Mammucari, C.; Pizzo, P. PSEN2 (presenilin 2) mutants linked to familial Alzheimer disease impair autophagy by altering Ca2+ homeostasis. Autophagy 2019, 15, 2044–2062. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Azimi, M.; Le, T.T.; Brown, N.L. Presenilin gene function and Notch signaling feedback regulation in the developing mouse lens. Differentiation 2018, 102, 40–52. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Nguyen, H.N.; Lee, M.S.; Hwang, D.Y.; Kim, Y.K.; Yoon, D.Y.; Lee, J.W.; Yun, Y.P.; Lee, M.K.; Oh, K.W.; Hong, J.T. Mutant presenilin 2 increased oxidative stress and p53 expression in neuronal cells. Biochem. Biophys. Res. Commun. 2007, 357, 174–180. [Google Scholar] [CrossRef] [PubMed]
- Walker, E.S.; Martinez, M.; Brunkan, A.L.; Goate, A. Presenilin 2 familial Alzheimer’s disease mutations result in partial loss of function and dramatic changes in Abeta 42/40 ratios. J. Neurochem. 2005, 92, 294–301. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.M.; Kang, D.W.; Um, Y.H.; Kim, S.; Lee, C.U.; Scheltens, P.; Lim, H.K. Plasma Oligomer β-Amyloid and White Matter Microstructural Integrity in Cognitively Normal Older Adults According to Cerebral Amyloid Deposition. J. Prev. Alzheimers Dis. 2023, 10, 837–846. [Google Scholar] [CrossRef] [PubMed]
- Dominguez, J.C.; Yu, J.R.T.; De Guzman, M.F.; Ampil, E.; Guevarra, A.C.; Joson, M.L.; Reandelar, M., Jr.; Martinez, M.S.; Ligsay, A.; Ocampo, F.; et al. Multimer Detection System-Oligomerized Amyloid Beta (MDS-OAβ): A Plasma-Based Biomarker Differentiates Alzheimer’s Disease from Other Etiologies of Dementia. Int. J. Alzheimers Dis. 2022, 2022, 9960832. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Pyun, J.M.; Ryu, J.S.; Lee, R.; Shim, K.H.; Youn, Y.C.; Ryoo, N.; Han, S.W.; Park, Y.H.; Kang, S.; An, S.S.A.; et al. Plasma Amyloid-β Oligomerization Tendency Predicts Amyloid PET Positivity. Clin. Interv. Aging 2021, 16, 749–755. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Shim, K.H.; Kim, D.; Kang, M.J.; Pyun, J.M.; Park, Y.H.; Youn, Y.C.; Park, K.W.; Suk, K.; Lee, H.W.; Gomes, B.F.; et al. Subsequent correlated changes in complement component 3 and amyloid beta oligomers in the blood of patients with Alzheimer’s disease. Alzheimers Dement. 2024, 20, 2731–2741. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Mirdita, M.; Schütze, K.; Moriwaki, Y.; Heo, L.; Ovchinnikov, S.; Steinegger, M. ColabFold: Making protein folding accessible to all. Nat. Methods 2022, 19, 679–682. [Google Scholar] [CrossRef] [PubMed]
- Zekanowski, C.; Styczyńska, M.; Pepłońska, B.; Gabryelewicz, T.; Religa, D.; Ilkowski, J.; Kijanowska-Haładyna, B.; Kotapka-Minc, S.; Mikkelsen, S.; Pfeffer, A.; et al. Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer’s disease in Poland. Exp. Neurol. 2003, 184, 991–996. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.H.; Kahn, A.; Cheng, R.; Reitz, C.; Vardarajan, B.; Lantigua, R.; Medrano, M.; Jiménez-Velázquez, I.Z.; Williamson, J.; Nagy, P.; et al. Disease-related mutations among Caribbean Hispanics with familial dementia. Mol. Genet. Genom. Med. 2014, 2, 430–437. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Hsu, S.; Pimenova, A.A.; Hayes, K.; Villa, J.A.; Rosene, M.J.; Jere, M.; Goate, A.M.; Karch, C.M. Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2. Neurobiol. Dis. 2020, 139, 104817. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Sassi, C.; Guerreiro, R.; Gibbs, R.; Ding, J.; Lupton, M.K.; Troakes, C.; Al-Sarraj, S.; Niblock, M.; Gallo, J.M.; Adnan, J.; et al. Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer’s disease. Neurobiol. Aging 2014, 35, 2881.e1–2881.e6. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Sala Frigerio, C.; Lau, P.; Troakes, C.; Deramecourt, V.; Gele, P.; Van Loo, P.; Voet, T.; De Strooper, B. On the identification of low allele frequency mosaic mutations in the brains of Alzheimer’s disease patients. Alzheimers Dement. 2015, 11, 1265–1276. [Google Scholar] [CrossRef] [PubMed]
- Wright, C.A.; Taylor, J.W.; Cochran, M.; Lawlor, J.M.J.; Moyers, B.A.; Amaral, M.D.; Bonnstetter, Z.T.; Carter, P.; Solomon, V.; Myers, R.M.; et al. Contributions of rare and common variation to early-onset and atypical dementia risk. Mol. Case Stud. 2023, 9, a006271. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Wang, D.; Scalici, A.; Wang, Y.; Lin, H.; Pitsillides, A.; Heard-Costa, N.; Cruchaga, C.; Ziegemeier, E.; Bis, J.C.; Fornage, M.; et al. Frequency of Variants in Mendelian Alzheimer’s Disease Genes within the Alzheimer’s Disease Sequencing Project (ADSP). medRxiv, 2024; preprint. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Hsu, S.; Gordon, B.A.; Hornbeck, R.; Norton, J.B.; Levitch, D.; Louden, A.; Ziegemeier, E.; Laforce, R., Jr.; Chhatwal, J.; Day, G.S.; et al. Karch CM. Discovery and validation of autosomal dominant Alzheimer’s disease mutations. Alzheimers Res. Ther. 2018, 10, 67. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Blauwendraat, C.; Wilke, C.; Jansen, I.E.; Schulte, C.; Simón-Sánchez, J.; Metzger, F.G.; Bender, B.; Gasser, T.; Maetzler, W.; Rizzu, P.; et al. Pilot whole-exome sequencing of a German early-onset Alzheimer’s disease cohort reveals a substantial frequency of PSEN2 variants. Neurobiol. Aging 2016, 37, 208.e11–208.e17. [Google Scholar] [CrossRef] [PubMed]
- Fernández, M.V.; Kim, J.H.; Budde, J.P.; Black, K.; Medvedeva, A.; Saef, B.; Deming, Y.; Del-Aguila, J.; Ibañez, L.; Dube, U.; et al. Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease. PLoS Genet. 2017, 13, e1007045. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Testi, S.; Fabrizi, G.M.; Pompanin, S.; Cagnin, A. Autosomal dominant Alzheimer’s disease with early frontal lobe involvement associated with the Met239Ile mutation of Presenilin 2 gene. J. Alzheimers Dis. 2012, 31, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Tremolizzo, L.; Susani, E.; Mapelli, C.; Isella, V.; Bertola, F.; Ferrarese, C.; Appollonio, I. First report of PSEN2 mutation presenting as posterior cortical atrophy. Alzheimer Dis. Assoc. Disord. 2015, 29, 249–251. [Google Scholar] [CrossRef] [PubMed]
- Llibre-Guerra, J.J.; Li, Y.; Allegri, R.F.; Mendez, P.C.; Surace, E.I.; Llibre-Rodriguez, J.J.; Sosa, A.L.; Aláez-Verson, C.; Longoria, E.M.; Tellez, A.; et al. Dominantly inherited Alzheimer’s disease in Latin America: Genetic heterogeneity and clinical phenotypes. Alzheimers Dement. 2021, 17, 653–664. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Jiao, B.; Liu, H.; Guo, L.; Xiao, X.; Liao, X.; Zhou, Y.; Weng, L.; Zhou, L.; Wang, X.; Jiang, Y.; et al. The role of genetics in neurodegenerative dementia: A large cohort study in South China. npj Genom. Med. 2021, 6, 69. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Li, X.Y.; Cui, Y.; Jing, D.; Xie, K.; Zhong, X.; Kong, Y.; Wang, Y.; Chu, M.; Wang, C.; Wu, L. Novel PSEN1 and PSEN2 Mutations Identified in Sporadic Early-onset Alzheimer Disease and Posterior Cortical Atrophy. Alzheimer Dis. Assoc. Disord. 2021, 35, 208–213. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Mao, C.; Li, J.; Dong, L.; Huang, X.; Lei, D.; Wang, J.; Chu, S.; Liu, C.; Peng, B.; Román, G.C.; et al. Clinical Phenotype and Mutation Spectrum of Alzheimer’s Disease with Causative Genetic Mutation in a Chinese Cohort. Curr. Alzheimer Res. 2021, 18, 265–272. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Zatti, G.; Burgo, A.; Giacomello, M.; Barbiero, L.; Ghidoni, R.; Sinigaglia, G.; Florean, C.; Bagnoli, S.; Binetti, G.; Sorbi, S.; et al. Presenilin mutations linked to familial Alzheimer’s disease reduce endoplasmic reticulum and Golgi apparatus calcium levels. Cell Calcium 2006, 39, 539–550. [Google Scholar] [CrossRef] [PubMed]
- Wallon, D.; Rousseau, S.; Rovelet-Lecrux, A.; Quillard-Muraine, M.; Guyant-Maréchal, L.; Martinaud, O.; Pariente, J.; Puel, M.; Rollin-Sillaire, A.; Pasquier, F.; et al. The French series of autosomal dominant early onset Alzheimer’s disease cases: Mutation spectrum and cerebrospinal fluid biomarkers. J. Alzheimers Dis. 2012, 30, 847–856. [Google Scholar] [CrossRef] [PubMed]
- Nicolas, G.; Wallon, D.; Charbonnier, C.; Quenez, O.; Rousseau, S.; Richard, A.C.; Rovelet-Lecrux, A.; Coutant, S.; Le Guennec, K.; Bacq, D.; et al. Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: Input and lessons. Eur. J. Hum. Genet. 2016, 24, 710–716. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Watanabe, N.; Tomita, T.; Sato, C.; Kitamura, T.; Morohashi, Y.; Iwatsubo, T. Pen-2 is incorporated into the gamma-secretase complex through binding to transmembrane domain 4 of presenilin 1. J. Biol. Chem. 2005, 280, 41967–41975. [Google Scholar] [CrossRef] [PubMed]
- Zoltowska, K.M.; Berezovska, O. Dynamic Nature of presenilin1/γ-Secretase: Implication for Alzheimer’s Disease Pathogenesis. Mol. Neurobiol. 2018, 55, 2275–2284. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Colijn, M.A.; Ismail, Z. Presenilin Gene Mutation-associated Psychosis: Phenotypic Characteristics and Clinical Implications. Alzheimer Dis. Assoc. Disord. 2024, 38, 101–106. [Google Scholar] [CrossRef]
- Jayadev, S.; Leverenz, J.B.; Steinbart, E.; Stahl, J.; Klunk, W.; Yu, C.E.; Bird, T.D. Alzheimer’s disease phenotypes and genotypes associated with mutations in presenilin 2. Brain 2010, 133 Pt 4, 1143–1154. [Google Scholar] [CrossRef] [PubMed]
- Tomaino, C.; Bernardi, L.; Anfossi, M.; Costanzo, A.; Ferrise, F.; Gallo, M.; Geracitano, S.; Maletta, R.; Curcio, S.A.; Mirabelli, M.; et al. Presenilin 2 Ser130Leu mutation in a case of late-onset “sporadic” Alzheimer’s disease. J. Neurol. 2007, 254, 391–393. [Google Scholar] [CrossRef] [PubMed]
- Wong, T.H.; Seelaar, H.; Melhem, S.; Rozemuller, A.J.M.; van Swieten, J.C. Genetic screening in early-onset Alzheimer’s disease identified three novel presenilin mutations. Neurobiol. Aging 2020, 86, 201.e9–201.e14. [Google Scholar] [CrossRef] [PubMed]
- Avramopoulos, D.; Fallin, M.D.; Bassett, S.S. Linkage to chromosome 14q in Alzheimer’s disease (AD) patients without psychotic symptoms. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2005, 132, 9–13. [Google Scholar] [CrossRef] [PubMed]
- Sinclair, L.I.; Kumar, A.; Darreh-Shori, T.; Love, S. Visual hallucinations in Alzheimer’s disease do not seem to be associated with chronic hypoperfusion of to visual processing areas V2 and V3 but may be associated with reduced cholinergic input to these areas. Alzheimers Res. Ther. 2019, 11, 80. [Google Scholar] [CrossRef] [PubMed]
- DeChellis-Marks, M.R.; Wei, Y.; Ding, Y.; Wolfe, C.M.; Krivinko, J.M.; MacDonald, M.L.; Lopez, O.L.; Sweet, R.A.; Kofler, J. Psychosis in Alzheimer’s Disease Is Associated with Increased Excitatory Neuron Vulnerability and Post-transcriptional Mechanisms Altering Synaptic Protein Levels. Front. Neurol. 2022, 13, 778419. [Google Scholar] [CrossRef] [PubMed]
- El Haj, M.; Roche, J.; Jardri, R.; Kapogiannis, D.; Gallouj, K.; Antoine, P. Clinical and neurocognitive aspects of hallucinations in Alzheimer’s disease. Neurosci. Biobehav. Rev. 2017, 83, 713–720. [Google Scholar] [CrossRef]
- Selkoe, D.J. Presenilin, Notch, and the genesis and treatment of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 2001, 98, 11039–11041. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Yoshida, S.; Kido, J.; Matsumoto, S.; Momosaki, K.; Mitsubuchi, H.; Shimazu, T.; Sugawara, K.; Endo, F.; Nakamura, K. Prenatal diagnosis of Gaucher disease using next-generation sequencing. Pediatr. Int. 2016, 58, 946–949. [Google Scholar] [CrossRef] [PubMed]
- Kilpatrick, B.S.; Magalhaes, J.; Beavan, M.S.; McNeill, A.; Gegg, M.E.; Cleeter, M.W.; Bloor-Young, D.; Churchill, G.C.; Duchen, M.R.; Schapira, A.H.; et al. Endoplasmic reticulum and lysosomal Ca2+ stores are remodelled in GBA1-linked Parkinson disease patient fibroblasts. Cell Calcium 2016, 59, 12–20. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Marchetti, B. Wnt/β-Catenin Signaling Pathway Governs a Full Program for Dopaminergic Neuron Survival, Neurorescue and Regeneration in the MPTP Mouse Model of Parkinson’s Disease. Int. J. Mol. Sci. 2018, 19, 3743. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Boonen, R.A.; van Tijn, P.; Zivkovic, D. Wnt signaling in Alzheimer’s disease: Up or down, that is the question. Ageing Res. Rev. 2009, 8, 71–82. [Google Scholar] [CrossRef] [PubMed]
- Kostes, W.W.; Brafman, D.A. The Multifaceted Role of WNT Signaling in Alzheimer’s Disease Onset and Age-Related Progression. Cells 2023, 12, 1204. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Pizzo, P.; Basso, E.; Filadi, R.; Greotti, E.; Leparulo, A.; Pendin, D.; Redolfi, N.; Rossini, M.; Vajente, N.; Pozzan, T.; et al. Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks. Cells 2020, 9, 2166. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Rossi, A.; Galla, L.; Gomiero, C.; Zentilin, L.; Giacca, M.; Giorgio, V.; Calì, T.; Pozzan, T.; Greotti, E.; Pizzo, P. Calcium Signaling and Mitochondrial Function in Presenilin 2 Knock-Out Mice: Looking for Any Loss-of-Function Phenotype Related to Alzheimer’s Disease. Cells 2021, 10, 204. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Gegg, M.E.; Schapira, A.H.V. The role of glucocerebrosidase in Parkinson disease pathogenesis. FEBS J. 2018, 285, 3591–3603. [Google Scholar] [CrossRef] [PubMed]
- Rohl, C.A.; Fiori, W.; Baldwin, R.L. Alanine is helix-stabilizing in both template-nucleated and standard peptide helices. Proc. Natl. Acad. Sci. USA 1999, 96, 3682–3687. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Lyu, P.C.; Sherman, J.C.; Chen, A.; Kallenbach, N.R. Alpha-helix stabilization by natural and unnatural amino acids with alkyl side chains. Proc. Natl. Acad. Sci. USA 1991, 88, 5317–5320. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Yang, Y.; Bagyinszky, E.; An, S.S.A. Patient with PSEN1 Glu318Gly and Other Possible Disease Risk Mutations, Diagnosed with Early Onset Alzheimer’s Disease. Int. J. Mol. Sci. 2023, 24, 15461. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Bagyinszky, E.; Kim, M.; Park, Y.H.; An, S.S.A.; Kim, S. PSEN1 His214Asn Mutation in a Korean Patient with Familial EOAD and the Importance of Histidine-Tryptophan Interactions in TM-4 Stability. Int. J. Mol. Sci. 2023, 25, 116. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Yang, Y.; Bagyinszky, E.; An, S.S.A. A Novel Rare PSEN2 Val226Ala in PSEN2 in a Korean Patient with Atypical Alzheimer’s Disease, and the Importance of PSEN2 5th Transmembrane Domain (TM5) in AD Pathogenesis. Int. J. Mol. Sci. 2024, 25, 9678. https://doi.org/10.3390/ijms25179678
Yang Y, Bagyinszky E, An SSA. A Novel Rare PSEN2 Val226Ala in PSEN2 in a Korean Patient with Atypical Alzheimer’s Disease, and the Importance of PSEN2 5th Transmembrane Domain (TM5) in AD Pathogenesis. International Journal of Molecular Sciences. 2024; 25(17):9678. https://doi.org/10.3390/ijms25179678
Chicago/Turabian StyleYang, YoungSoon, Eva Bagyinszky, and Seong Soo A. An. 2024. "A Novel Rare PSEN2 Val226Ala in PSEN2 in a Korean Patient with Atypical Alzheimer’s Disease, and the Importance of PSEN2 5th Transmembrane Domain (TM5) in AD Pathogenesis" International Journal of Molecular Sciences 25, no. 17: 9678. https://doi.org/10.3390/ijms25179678