ABCA7, a Genetic Risk Factor Associated with Alzheimer’s Disease Risk in African Americans

2022 ◽  
pp. 1-15
Author(s):  
Kaitlyn E. Stepler ◽  
Taneisha R. Gillyard ◽  
Calla B. Reed ◽  
Tyra M. Avery ◽  
Jamaine S. Davis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
African American ◽  
Amyloid Beta ◽  
Disease Risk ◽  
African Ancestry ◽  
European Ancestry ◽  
Black Adults ◽  
American Black ◽  
The Impact

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.

scholarly journals Inclusion of African American/Black adults in a pilot brain proteomics study of Alzheimer's disease

2020 ◽  
Vol 146 ◽  
pp. 105129 ◽  
Author(s):  
Kaitlyn E. Stepler ◽  
Emily R. Mahoney ◽  
Julia Kofler ◽  
Timothy J. Hohman ◽  
Oscar L. Lopez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
African American ◽  
Black Adults ◽  
Proteomics Study ◽  
American Black

scholarly journals The Impact of Amyloid-Beta Positivity with 18F-Florbetaben PET on Neuropsychological Aspects in Parkinson’s Disease Dementia

Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 380
Author(s):  
Seunghee Na ◽  
Hyeonseok Jeong ◽  
Jong-Sik Park ◽  
Yong-An Chung ◽  
In-Uk Song
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Amyloid Beta ◽  
Neuropsychiatric Symptoms ◽  
Amyloid Pet ◽  
Motor Symptoms ◽  
Parkinson’S Disease Dementia ◽  
The Impact

The neuropathology of Parkinson’s disease dementia (PDD) is heterogenous, and the impacts of each pathophysiology and their synergistic effects are not fully understood. The aim of this study was to evaluate the frequency and impacts of co-existence with Alzheimer’s disease in patients with PDD by using 18F-florbetaben PET imaging. A total of 23 patients with PDD participated in the study. All participants underwent 18F-florbetaben PET and completed a standardized neuropsychological battery and assessment of motor symptoms. The results of cognitive tests, neuropsychiatric symptoms, and motor symptoms were analyzed between the positive and negative 18F-florbetaben PET groups. Four patients (17.4%) showed significant amyloid burden. Patients with amyloid-beta showed poorer performance in executive function and more severe neuropsychiatric symptoms than those without amyloid-beta. Motor symptoms assessed by UPDRS part III and the modified H&Y Scale were not different between the two groups. The amyloid PET scan of a patient with PDD can effectively reflect a co-existing Alzheimer’s disease pathology. Amyloid PET scans might be able to help physicians of PDD patients showing rapid progression or severe cognitive/behavioral features.

scholarly journals Advancing Alzheimer’s Disease Care and Services Among Racial and Ethnic Minorities

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 745-745
Author(s):  
Lenora Smith ◽  
Roland Thorpe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
African American ◽  
Ethnic Minorities ◽  
Health Care Expenditures ◽  
Racial And Ethnic Minorities ◽  
Care Services ◽  
Study Results ◽  
Using Data ◽  
The Impact

Abstract Research shows consistent and adverse disparities among racial and ethnic minorities compared to non-Hispanic Whites in the prevalence and incidence of Alzheimer’s disease, mortality, participation in clinical trials, use of medications and other interventions, health care expenditures, and quality-of-life outcomes. The literature suggests numerous underlying causes, including factors related to measurement of the disease, genetics, socioeconomic factors, cultural differences, lack of culturally competent interventions, and discrimination in services and care. Although these disparities are well known, little is known about the effectiveness of various strategies to address these differences within the context of Alzheimer’s disease services and care. This symposium aims to contribute to this knowledge. The first presentation examines the role of race with marital status and risk for dementia using data from the Health and Retirement Study. Results suggest differences for unmarried White and unmarried older adults of color, which can inform dementia care services. The second presentation highlights the opportunities and challenges of facilitating cognitive impairment screenings among African American congregations. The third presentation introduces attitudes about brain donation among African American research participants and suggestions to increase involvement. The symposium concludes with a presentation on hearing care disparities in dementia with practical recommendations on how to close this gap in hearing care. The findings from these papers contribute significantly to the impact of ethnoracial differences in dementia and the need to include more diverse populations in ADRD research to promote equity. Alzheimer’s Disease Research Interest Group Sponsored Symposium.

scholarly journals Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta

Neuron ◽  
2013 ◽  
Vol 78 (4) ◽  
pp. 631-643 ◽  
Author(s):  
Ana Griciuc ◽  
Alberto Serrano-Pozo ◽  
Antonio R. Parrado ◽  
Andrea N. Lesinski ◽  
Caroline N. Asselin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Disease Risk ◽  
Risk Gene

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

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

The impact of age and Alzheimer’s disease risk factors on memory performance over time

Aging Health ◽  
2013 ◽  
Vol 9 (1) ◽  
pp. 115-124 ◽  
Author(s):  
Natalie C Kaiser ◽  
Karen J Miller ◽  
Prabha Siddarth ◽  
Linda M Ercoli ◽  
Gary W Small
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Risk ◽  
Memory Performance ◽  
The Impact ◽  
Over Time

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

2012 ◽  
Vol 8 (4S_Part_15) ◽  
pp. P549-P550
Author(s):  
Mariet Allen ◽  
Otto Pedraza ◽  
Thuy Nguyen ◽  
Gina Bisceglio ◽  
Seleeke Flingai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
African American ◽  
Disease Risk ◽  
Case Control ◽  
Control Series ◽  
Risk Snps ◽  
American Case ◽  
African American Case

scholarly journals Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jong-Ho Park ◽  
Inho Park ◽  
Emilia Moonkyung Youm ◽  
Sejoon Lee ◽  
June-Hee Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Disease Risk ◽  
Association Studies ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Ε4 Allele

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disease associated with a complex genetic etiology. Besides the apolipoprotein E ε4 (APOE ε4) allele, a few dozen other genetic loci associated with AD have been identified through genome-wide association studies (GWAS) conducted mainly in individuals of European ancestry. Recently, several GWAS performed in other ethnic groups have shown the importance of replicating studies that identify previously established risk loci and searching for novel risk loci. APOE-stratified GWAS have yielded novel AD risk loci that might be masked by, or be dependent on, APOE alleles. We performed whole-genome sequencing (WGS) on DNA from blood samples of 331 AD patients and 169 elderly controls of Korean ethnicity who were APOE ε4 carriers. Based on WGS data, we designed a customized AD chip (cAD chip) for further analysis on an independent set of 543 AD patients and 894 elderly controls of the same ethnicity, regardless of their APOE ε4 allele status. Combined analysis of WGS and cAD chip data revealed that SNPs rs1890078 (P = 6.64E−07) and rs12594991 (P = 2.03E−07) in SORCS1 and CHD2 genes, respectively, are novel genetic variants among APOE ε4 carriers in the Korean population. In addition, nine possible novel variants that were rare in individuals of European ancestry but common in East Asia were identified. This study demonstrates that APOE-stratified analysis is important for understanding the genetic background of AD in different populations.

scholarly journals Imbalances in Copper or Zinc Concentrations Trigger Further Trace Metal Dyshomeostasis in Amyloid-Beta Producing Caenorhabditis elegans

2021 ◽  
Vol 15 ◽  
Author(s):  
Ada Metaxas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Trace Metals ◽  
Trace Metal ◽  
Amyloid Beta ◽  
Model Organism ◽  
Return To Equilibrium ◽  
C Elegans ◽  
Copper And Zinc ◽  
The Impact

Alzheimer's Disease (AD), a progressive neurodegenerative disease characterized by the buildup of amyloid-beta (Aβ) plaques, is believed to be a disease of trace metal dyshomeostasis. Amyloid-beta is known to bind with high affinity to trace metals copper and zinc. This binding is believed to cause a conformational change in Aβ, transforming Aβ into a configuration more amenable to forming aggregations. Currently, the impact of Aβ-trace metal binding on trace metal homeostasis and the role of trace metals copper and zinc as deleterious or beneficial in AD remain elusive. Given that Alzheimer's Disease is the sixth leading cause of adult death in the U.S., elucidating the molecular interactions that characterize Alzheimer's Disease pathogenesis will allow for better treatment options. To that end, the model organism C. elegans is used in this study. C. elegans, a transparent nematode whose connectome has been fully established, is an amenable model to study AD phenomena using a multi-layered, interconnected approach. Aβ-producing and non-Aβ-producing C. elegans were individually supplemented with copper and zinc. On day 6 and day 9 after synchronization, the percent of worms paralyzed, concentration of copper, and concentration of zinc were measured in both groups of worms. This study demonstrates that dyshomeostasis of trace metals copper or zinc triggers further trace metal dyshomeostasis in Aβ-producing worms, while dyshomeostasis of copper or zinc triggers a return to equilibrium in non-Aβ-producing worms. This supports the characterization of Alzheimer's Disease as a disease of trace metal dyshomeostasis.

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