LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry

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2 Scopus citations

Abstract

Limbic-predominant age-related TDP-43 encephalopathy (LATE) affects approximately one-third of older individuals and is associated with cognitive impairment. However, there is a highly incomplete understanding of the genetic determinants of LATE neuropathologic changes (LATE-NC) in diverse populations. The defining neuropathologic feature of LATE-NC is TDP-43 proteinopathy, often with comorbid hippocampal sclerosis (HS). In terms of genetic risk factors, LATE-NC and/or HS are associated with single nucleotide variants (SNVs) in 3 genes - TMEM106B (rs1990622), GRN (rs5848), and ABCC9 (rs1914361 and rs701478). We evaluated these 3 genes in convenience samples of individuals of African ancestry. The allele frequencies of the LATE-associated alleles were significantly different between persons of primarily African (versus European) ancestry: In persons of African ancestry, the risk-associated alleles for TMEM106B and ABCC9 were less frequent, whereas the risk allele in GRN was more frequent. We performed an exploratory analysis of data from African-American subjects processed by the Alzheimer's Disease Genomics Consortium, with a subset of African-American participants (n = 166) having corroborating neuropathologic data through the National Alzheimer's Coordinating Center (NACC). In this limited-size sample, the ABCC9/rs1914361 SNV was associated with HS pathology. More work is required concerning the genetic factors influencing non-Alzheimer disease pathology such as LATE-NC in diverse cohorts.

Original languageEnglish
Pages (from-to)760-768
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume82
Issue number9
DOIs
StatePublished - Sep 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s).

Keywords

  • Dementia
  • Diversity
  • Epidemiology
  • FTLD
  • Genome-Wide Association Studies (GWAS)
  • KATP
  • KCNMB2

ASJC Scopus subject areas

  • General Medicine

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