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

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...

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Vydáno v:	Journal of neuropathology and experimental neurology Ročník 82; číslo 9; s. 760 - 768
Hlavní autoři:	Katsumata, Yuriko, Fardo, David W, Shade, Lincoln M P, Nelson, Peter T
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Oxford University Press 01.09.2023
Témata:	African Americans Aging - pathology Alleles Allelomorphism Alzheimer Disease - genetics Alzheimer Disease - pathology Cognition disorders Degeneration Dementia Genetic aspects Genetic variation Genomics Health aspects Health risk assessment Humans Membrane Proteins - genetics Nerve Tissue Proteins - genetics Nervous system Neurological research Neuropathology Original Polymorphism, Single Nucleotide - genetics Progranulins - genetics Risk factors Sulfonylurea Receptors - genetics TDP-43 Proteinopathies - pathology United States KATP Genome-Wide Association Studies (GWAS) Epidemiology Diversity FTLD Dementia KCNMB2
ISSN:	0022-3069, 1554-6578, 1554-6578
On-line přístup:	Získat plný text
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0022-3069 1554-6578 1554-6578
DOI:	10.1093/jnen/nlad059