P3-257: Investigation of established Alzheimer's disease-risk SNPs for association with Alzheimer's disease in an African-American case control series

African American/Black adults are twice as likely to have Alzheimer’s disease (AD) compared to non-Hispanic White adults. Genetics partially contributes to this disparity in AD risk, among other factors, as there are several genetic variants associated with AD that are more prevalent in individuals of African or European ancestry. The phospholipid-transporting ATPase ABCA7 (ABCA7) gene has stronger associations with AD risk in individuals with African ancestry than in individuals with European ancestry. In fact, ABCA7 has been shown to have a stronger effect size than the apolipoprotein E (APOE) ɛ4 allele in African American/Black adults. ABCA7 is a transmembrane protein involved in lipid homeostasis and phagocytosis. ABCA7 dysfunction is associated with increased amyloid-beta production, reduced amyloid-beta clearance, impaired microglial response to inflammation, and endoplasmic reticulum stress. This review explores the impact of ABCA7 mutations that increase AD risk in African American/Black adults on ABCA7 structure and function and their contributions to AD pathogenesis. The combination of biochemical/biophysical and ‘omics-based studies of these variants needed to elucidate their downstream impact and molecular contributions to AD pathogenesis is highlighted.

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Alzheimer's disease risk SNPs show no strong effect on miRNA expression in human lymphoblastoid cell lines

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2019.08.013 ◽

2020 ◽

Vol 86 ◽

pp. 202.e1-202.e3 ◽

Cited By ~ 1

Author(s):

Inken Wohlers ◽

Colin Schulz ◽

Fabian Kilpert ◽

Lars Bertram

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cell Lines ◽

Mirna Expression ◽

Disease Risk ◽

Lymphoblastoid Cell Lines ◽

Human Lymphoblastoid Cell ◽

Risk Snps ◽

Human Lymphoblastoid Cell Lines

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Investigation of an amyloid precursor protein protective mutation (A673T) in a North American case-control sample of late-onset Alzheimer's disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2014.01.020 ◽

2014 ◽

Vol 35 (7) ◽

pp. 1779.e15-1779.e16 ◽

Cited By ~ 19

Author(s):

Mikhil N. Bamne ◽

F. Yesim Demirci ◽

Sarah Berman ◽

Beth E. Snitz ◽

Samantha L. Rosenthal ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Precursor Protein ◽

North American ◽

Late Onset ◽

Control Sample ◽

Case Control ◽

Precursor Protein ◽

American Case

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P3-597: UNCOVERING NEW INTERVENTION STRATEGIES FOR MITIGATING ALZHEIMER'S DISEASE RISK IN FAITH-BASED, AFRICAN-AMERICAN COMMUNITIES

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.3634 ◽

2019 ◽

Vol 15 ◽

pp. P1204-P1205

Author(s):

Kristen B. Naney ◽

Grace Byfield ◽

Jia Ma ◽

Rosalind O. Pugh-Scott ◽

Takiyah D. Starks ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

African American ◽

Disease Risk ◽

Intervention Strategies ◽

Faith Based ◽

African American Communities

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Interaction between variants in CLU and MS4A4E modulates Alzheimer's disease risk

10.1101/028951 ◽

2015 ◽

Cited By ~ 2

Author(s):

Mark T. W. Ebbert ◽

Kevin L. Boehme ◽

Mark E. Wadsworth ◽

Lyndsay A. Staley ◽

Shubhabrata Mukherjee ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Risk ◽

Disease Incidence ◽

Population Attributable Fraction ◽

Dominant Effect ◽

Control Series ◽

Risk Alleles ◽

Causal Variants ◽

Meta Analyses

INTRODUCTION: Ebbert et al. reported gene-gene interactions between rs11136000-rs670139 (CLU-MS4A4E) and rs3865444-rs670139 (CD33-MS4A4E). We evaluate these interactions in the largest dataset for an epistasis study. METHODS: We tested interactions using 3837 cases and 4145 controls from ADGC using meta- and permutation analyses. We repeated meta-analyses stratified by APOEϵ4 status, estimated combined OR and population attributable fraction (cPAF), and explored causal variants. RESULTS: Results support the CLU-MS4A4E interaction and a dominant effect. An association between CLU-MS4A4E and APOEϵ4 negative status exists. The estimated synergy factor, OR, and cPAF for rs11136000-rs670139 are 2.23, 2.45 and 8.0, respectively. We identified potential causal variants. DISCUSSION: We replicated the CLU-MS4A4E interaction in a large case-control series, with APOEϵ4 and possible dominant effect. The CLU-MS4A4E OR is higher than any Alzheimer's disease locus except APOEϵ4, APP, and TREM2. We estimated an 8% decrease in Alzheimer's disease incidence without CLU-MS4A4E risk alleles and identified potential causal variants.

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