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Basic Science and Pathogenesis.

Danielle Luu1, Koral V Wheeler1, Maxwell W Hand1

  • 1Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.

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Genetic variants linked to tau accumulation in the brain were identified in non-Hispanic Black individuals. This finding may improve understanding of Alzheimer's disease risk across diverse populations.

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Area of Science:

  • Genetics
  • Neuroimaging
  • Alzheimer's Disease Research

Background:

  • Genetic variations impact Alzheimer's Disease (AD) risk and progression.
  • Specific gene influences on AD neuropathology, particularly tau accumulation, remain unclear across diverse ethnoracial groups.

Purpose of the Study:

  • To conduct a genome-wide association study (GWAS) across three ethnoracial groups.
  • To identify genetic variants associated with brain tau positron emission tomography (PET) signal in the medial temporal lobe (MTL).

Main Methods:

  • Analyzed data from 994 participants (Hispanic, non-Hispanic Black (NHB), non-Hispanic White (NHW)) from the Health and Aging Brain Study-Health Disparities (HABS-HD).
  • Utilized PI-2620 PET imaging to calculate tau standardized uptake value ratios (SUVRs) in the MTL.
  • Performed GWAS within each ethnoracial group, controlling for covariates and population structure.

Main Results:

  • Identified eleven variants reaching suggestive significance (p < 1.00x10^-5) across ethnoracial groups.
  • Discovered specific SNPs in the NHB sample associated with genes linked to hippocampal function, metabolic regulation, lipids, and inflammation, all implicated in AD risk.
  • Found separate variants in Hispanic and NHW samples, but these were not associated with known AD factors.

Conclusions:

  • Identified potential genetic variants associated with MTL tau accumulation in NHB participants, located in genes previously linked to AD risk factors.
  • These findings may enhance understanding of dementia risk across ethnoracial groups.
  • Results guide future research into personalized medicine and precision healthcare for AD.