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Advances in the Research of Alzheimer's Disease: From Molecular Basis to Therapy

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 11639

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Dr. Lilach Soreq

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Molecular Neuroscience Department, University College London, London, UK
Interests: ageing; Alzheimer’s disease; bioinformatics; RNA-Seq; Parkinson’s disease
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

Alzheimer’s disease is the most prevalent neurodegenerative disease worldwide, with an increasing number of new cases each year. It is estimated that there are currently 44 million people worldwide living with dementia, disproportionately affecting women. The disease is the currently the sixth leading cause of death in the united states, highlighting the essential need for a therapeutic treatment to slow or eradicate disease progression. This disease is molecularly characterized by biochemical lesions of amyloid β plaques and Tau tangles. Additionally, rare mutations in amyloid β protein, amyloid precursor protein, presenilin 1 and 2, ADAM10 and ADAM17 have been shown to triggers amyloid-beta accumulation and are sufficient to induce full biochemical and morphological signatures of Alzheimer’s disease.

In addition the role of amyloid β, diverse intracellular processes and neuronal cell-types are likely required for Alzheimer’s progression. Microgliall genes have been shown to have a central role in Alzheimer’s pathology as well.

Dr. Lilach Soreq
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (4 papers)

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Research

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22 pages, 11108 KiB

Open AccessArticle

Inducible and Conditional Activation of Adult Neurogenesis Rescues Cadmium-Induced Hippocampus-Dependent Memory Deficits in ApoE4-KI Mice

by Megumi T. Matsushita, Hao Wang, Glen M. Abel and Zhengui Xia

Int. J. Mol. Sci. 2023, 24(11), 9118; https://doi.org/10.3390/ijms24119118 - 23 May 2023

Cited by 2 | Viewed by 1254

Abstract

The apolipoprotein E (ApoE) gene is a genetic risk factor for late-onset Alzheimer’s disease, in which ε4 allele carriers have increased risk compared to the common ε3 carriers. Cadmium (Cd) is a toxic heavy metal and a potential neurotoxicant. We previously reported a gene–environment interaction (GxE) effect between ApoE4 and Cd that accelerates or increases the severity of the cognitive decline in ApoE4-knockin (ApoE4-KI) mice exposed to 0.6 mg/L CdCl₂ through drinking water compared to control ApoE3-KI mice. However, the mechanisms underlying this GxE effect are not yet defined. Because Cd impairs adult neurogenesis, we investigated whether genetic and conditional stimulation of adult neurogenesis can functionally rescue Cd-induced cognitive impairment in ApoE4-KI mice. We crossed either ApoE4-KI or ApoE3-KI to an inducible Cre mouse strain, Nestin-CreER^TM:caMEK5-eGFP^loxP/loxP (designated as caMEK5), to generate ApoE4-KI:caMEK5 and ApoE3-KI:caMEK5. Tamoxifen administration in these mice genetically and conditionally induces the expression of caMEK5 in adult neural stem/progenitor cells, enabling the stimulation of adult neurogenesis in the brain. Male ApoE4-KI:caMEK5 and ApoE3-KI:caMEK5 mice were exposed to 0.6 mg/L CdCl₂ throughout the experiment, and tamoxifen was administered once Cd-induced impairment in spatial working memory was consistently observed. Cd exposure impaired spatial working memory earlier in ApoE4-KI:caMEK5 than in ApoE3-KI:caMEK5 mice. In both strains, these deficits were rescued after tamoxifen treatment. Consistent with these behavioral findings, tamoxifen treatment enhanced adult neurogenesis by increasing the morphological complexity of adult-born immature neurons. These results provide evidence for a direct link between impaired spatial memory and adult neurogenesis in this GxE model. Full article

(This article belongs to the Special Issue Advances in the Research of Alzheimer's Disease: From Molecular Basis to Therapy)

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12 pages, 1412 KiB

Open AccessArticle

ADAM10 Gene Variants in AD Patients and Their Relationship to CSF Protein Levels

by Pablo Agüero-Rabes, Julián Pérez-Pérez, Lucía Cremades-Jimeno, María-Salud García-Ayllón, Adriana Gea-González, María José Sainz, Ignacio Mahillo-Fernández, Raquel Téllez, Blanca Cárdaba, Javier Sáez-Valero and Estrella Gómez-Tortosa

Int. J. Mol. Sci. 2023, 24(7), 6113; https://doi.org/10.3390/ijms24076113 - 24 Mar 2023

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Abstract

ADAM10 is the main α-secretase acting in the non-amyloidogenic processing of APP. We hypothesized that certain rare ADAM10 variants could increase the risk for AD by conferring the age-related downregulation of α-secretase. The ADAM10 gene was sequenced in 103 AD cases (82% familial) and 96 cognitively preserved nonagenarians. We examined rare variants (MAF < 0.01) and determined their potential association in the AD group with lower CSF protein levels, as analyzed by means of ELISA, and Western blot (species of 50 kDa, 55 kDa, and 80 kDa). Rare variants were found in 15.5% of AD cases (23% early-onset, 8% late-onset) and in 12.5% of nonagenarians, and some were group-specific. All were intronic variants except Q170H, found in three AD cases and one nonagenarian. The 3′UTR rs74016945 (MAF = 0.01) was found in 6% of the nonagenarians (OR 0.146, p = 0.057). Altogether, ADAM10 total levels or specific species were not significantly different when comparing AD with controls or carriers of rare variants versus non-carriers (except a Q170H carrier exhibiting low levels of all species), and did not differ according to the age at onset or APOE genotype. We conclude that ADAM10 exonic variants are uncommon in AD cases, and the presence of rare intronic variants (more frequent in early-onset cases) is not associated with decreased protein levels in CSF. Full article

(This article belongs to the Special Issue Advances in the Research of Alzheimer's Disease: From Molecular Basis to Therapy)

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Review

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29 pages, 1530 KiB

Open AccessReview

Topical Cellular/Tissue and Molecular Aspects Regarding Nonpharmacological Interventions in Alzheimer’s Disease—A Systematic Review

by Sorina Aurelian, Adela Ciobanu, Roxana Cărare, Simona-Isabelle Stoica, Aurelian Anghelescu, Vlad Ciobanu, Gelu Onose, Constantin Munteanu, Cristina Popescu, Ioana Andone, Aura Spînu, Carmen Firan, Ioana Simona Cazacu, Andreea-Iulia Trandafir, Mihai Băilă, Ruxandra-Luciana Postoiu and Andreea Zamfirescu

Int. J. Mol. Sci. 2023, 24(22), 16533; https://doi.org/10.3390/ijms242216533 - 20 Nov 2023

Cited by 2 | Viewed by 1302

Abstract

One of the most complex and challenging developments at the beginning of the third millennium is the alarming increase in demographic aging, mainly—but not exclusively—affecting developed countries. This reality results in one of the harsh medical, social, and economic consequences: the continuously increasing number of people with dementia, including Alzheimer’s disease (AD), which accounts for up to 80% of all such types of pathology. Its large and progressive disabling potential, which eventually leads to death, therefore represents an important public health matter, especially because there is no known cure for this disease. Consequently, periodic reappraisals of different therapeutic possibilities are necessary. For this purpose, we conducted this systematic literature review investigating nonpharmacological interventions for AD, including their currently known cellular and molecular action bases. This endeavor was based on the PRISMA method, by which we selected 116 eligible articles published during the last year. Because of the unfortunate lack of effective treatments for AD, it is necessary to enhance efforts toward identifying and improving various therapeutic and rehabilitative approaches, as well as related prophylactic measures. Full article

(This article belongs to the Special Issue Advances in the Research of Alzheimer's Disease: From Molecular Basis to Therapy)

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16 pages, 758 KiB

Open AccessReview

Neurotransmitters in Prevention and Treatment of Alzheimer’s Disease

by Zhenqi Yang, Yong Zou and Lifeng Wang

Int. J. Mol. Sci. 2023, 24(4), 3841; https://doi.org/10.3390/ijms24043841 - 14 Feb 2023

Cited by 9 | Viewed by 7227

Abstract

Alzheimer’s disease (AD) is the most frequent cause of cognitive impairment in middle-aged and older populations. There is a lack of drugs that demonstrate significant efficacy in AD, so the study of the pathogenesis of AD is of great importance. More efficacious interventions are needed, as reflected by our population’s fast aging. Synaptic plasticity is the capacity of neurons to adjust their connections, and it is strongly tied to learning and memory, cognitive function, and brain injury recovery. Changes in synaptic strength, such as long-term potentiation (LTP) or inhibition (LTD), are thought to represent the biological foundation of the early stages of learning and memory. The results of numerous studies confirm that neurotransmitters and their receptors play an important role in the regulation of synaptic plasticity. However, so far, there is no definite correlation between the function of neurotransmitters in aberrant neural oscillation and AD-related cognitive impairment. We summarized the AD process to understand the impact of neurotransmitters in the progression and pathogenesis of AD, including the current status of neurotransmitter target drugs, and the latest evidence of neurotransmitters’ function and changes in the AD process. Full article

(This article belongs to the Special Issue Advances in the Research of Alzheimer's Disease: From Molecular Basis to Therapy)

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