A Comprehensive Analysis of Unique and Recurrent Copy Number Variations in Alzheimer’s Disease and its Related Disorders

Background: Copy number variations (CNVs) play an important role in the genetic etiology of various neurological disorders including Alzheimer’s disease (AD). Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) were shown to share mechanisms and signaling pathways with AD. Objective: We aimed to assess CNVs regions that may harbor genes contributing to AD, T2DM and MDD in 67 Saudi familial and sporadic AD patients with no alterations in the known genes of AD and genotyped previously for APOE. Methods: DNA was analyzed using the CytoScan-HD array. Two layers of filtering criteria were applied. All the identified CNVs were checked in the Database of Genomic Variants (DGV). Results: A total of 1086 CNVs (565 gains and 521 losses) were identified in our study. We found 73 CNVs harboring genes that may be associated with AD, T2DM or MDD. Nineteen CNVs were novel. Most importantly, 42 CNVs were unique in our studied cohort existing only in one patient. Two large gains on chromosomes 1 and 13 harbored genes implicated in the studied disorders. We identified CNVs in genes that encode proteins involved in metabolism of amyloid-b peptide (AGRN, APBA2, CR1, CR2, IGF2R, KIAA0125, MBP, RER1, RTN4R, VDR and WISPI) or Tau proteins (CACNAIC, CELF2, DUSP22, HTRA1 and SLC2A14). Conclusion: The present work provided information on the presence of CNVs related to AD, T2DM and MDD in Saudi Alzheimer’s patients.

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In Silico Preliminary Association of Ammonia Metabolism Genes GLS, CPS1, and GLUL with Risk of Alzheimer’s Disease, Major Depressive Disorder, and Type 2 Diabetes

Journal of Molecular Neuroscience ◽

10.1007/s12031-018-1035-0 ◽

2018 ◽

Vol 64 (3) ◽

pp. 385-396 ◽

Cited By ~ 2

Author(s):

Jeddidiah W. D. Griffin ◽

Ying Liu ◽

Patrick C. Bradshaw ◽

Kesheng Wang

Keyword(s):

Alzheimer’S Disease ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

In Silico ◽

Major Depressive ◽

Ammonia Metabolism

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O3-06-01: WHOLE EXOME SEQUENCING STUDY IDENTIFIES RARE COPY NUMBER VARIATIONS FOR LATE-ONSET ALZHEIMER'S DISEASE: THE ALZHEIMER'S DISEASE SEQUENCING PROJECT CASE-CONTROL ANALYSIS

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.2800 ◽

2006 ◽

Vol 14 (7S_Part_19) ◽

pp. P1025-P1025

Author(s):

Xueqiu Jian ◽

Theodore Chiang ◽

Kim C. Worley ◽

Joshua C. Bis ◽

Anita L. Destefano ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Copy Number ◽

Late Onset ◽

Case Control ◽

Copy Number Variations ◽

Control Analysis ◽

Sequencing Project ◽

Whole Exome ◽

Case Control Analysis

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Rare autosomal copy number variations in early-onset familial Alzheimer’s disease

Molecular Psychiatry ◽

10.1038/mp.2013.77 ◽

2013 ◽

Vol 19 (6) ◽

pp. 676-681 ◽

Cited By ~ 51

Author(s):

B V Hooli ◽

Z M Kovacs-Vajna ◽

K Mullin ◽

M A Blumenthal ◽

M Mattheisen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Copy Number ◽

Copy Number Variations ◽

Familial Alzheimer’S Disease ◽

Autosomal Copy ◽

Familial Alzheimer's Disease

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GSK-3 Inhibitors: A new class of drugs for Alzheimer's Disease Treatment

Current Drug Targets ◽

10.2174/1389450122666210114095307 ◽

2021 ◽

Vol 22 ◽

Author(s):

Dilipkumar Pal ◽

Souvik Mukherjee ◽

In-ho Song ◽

Satish Balasaheb Nimse

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Tau Proteins ◽

Drug Candidates ◽

New Class ◽

Drug Molecules ◽

Function Impairment ◽

Relationship Of ◽

Novel Drug

: Alzheimer's disease (AD), a chronic neurodegenerative disease, is the most common form of dementia that causes cognitive function impairment, including memory, thinking, and behavioral changes that ultimately lead to death. The over activation of GSK-3, an enzyme from the proline/serine Ki NS family, has been associated with hyper-phosphorylation of tau proteins. Hyper-phosphorylated tau proteins self-assemble to form tangles of straight and helical filaments are known to be involved in AD. Therefore, GSK-3 has been considered a potential target of novel drug discovery for AD treatment. The research on the development of GSK-3 inhibitors has received enormous attention from the vast scientific community because they are targeted for AD and other diseases, including type 2 diabetes, cancers, stroke, Parkinson's disease, bipolar disorder etc. Various drugs originated from synthetic and natural origins have been designed to inhibit GSK-3 activity. However, there is a need to develop novel drug candidates that are selective in the inhibition of GSK3. Hence, this review summarizes the potential of GSK-3 inhibitors for AD therapy. The structure-activity relationship of current drug molecules and the potential problems associated with them are discussed in detail.

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