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Journal of Alzheimer's disease : JAD
2022;86 (1): 5-19.

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

Kaitlyn E Stepler, Taneisha R Gillyard, Calla B Reed, Tyra M Avery, Jamaine S Davis, Renã A S Robinson
Author Information
  1. Kaitlyn E Stepler: Department of Chemistry, Vanderbilt University, Nashville, TN, USA.
  2. Taneisha R Gillyard: Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN, USA.
  3. Calla B Reed: Department of Chemistry, Vanderbilt University, Nashville, TN, USA.
  4. Tyra M Avery: Department of Life and Physical Sciences, Fisk University, Nashville, TN, USA.
  5. Jamaine S Davis: Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN, USA.
  6. Renã A S Robinson: Department of Chemistry, Vanderbilt University, Nashville, TN, USA.
PMID: 35034901 DOI: 10.3233/JAD-215306

Abstract

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.

Keywords

African Americans Alzheimer’s disease Blacks health status disparities human ABCA7 protein proteomics single nucleotide polymorphism subfamily A of ATP binding cassette transporter

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Grants

  1. T32 AG058524/NIA NIH HHS
  2. U54 MD007586/NIMHD NIH HHS

MeSH Term

ATP-Binding Cassette Transporters
Black or African American
Alzheimer Disease
Amyloid beta-Peptides
Humans
Risk Factors

Chemicals

ABCA7 protein, human
ATP-Binding Cassette Transporters
Amyloid beta-Peptides
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review
Article has an altmetric score of 19

Word Cloud

Created with Highcharts 10.0.0ABCA7AfricanADadultsAmerican/BlackriskindividualsancestryAlzheimer'sdiseasevariantsassociatedEuropeanstrongerproteinamyloid-betaimpactcontributionspathogenesisRiskAmericanstwicelikelycomparednon-HispanicWhiteGeneticspartiallycontributesdisparityamongfactorsseveralgeneticprevalentphospholipid-transportingATPasegeneassociationsfactshowneffectsizeapolipoproteinEAPOEɛ4alleletransmembraneinvolvedlipidhomeostasisphagocytosisdysfunctionincreasedproductionreducedclearanceimpairedmicroglialresponseinflammationendoplasmicreticulumstressreviewexploresmutationsincreasestructurefunctioncombinationbiochemical/biophysical'omics-basedstudiesneededelucidatedownstreammolecularhighlightedGeneticFactorAssociatedDiseaseAlzheimer’sBlackshealthstatusdisparitieshumanproteomicssinglenucleotidepolymorphismsubfamilyATPbindingcassettetransporter

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