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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Veröffentlicht in:Journal of neuropathology and experimental neurology Jg. 82; H. 9; S. 760 - 768
Hauptverfasser: Katsumata, Yuriko, Fardo, David W, Shade, Lincoln M P, Nelson, Peter T
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Oxford University Press 01.09.2023
Schlagworte:
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
Online-Zugang:Volltext
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Abstract 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.
AbstractList 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.
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. KEYWORDS: Dementia, Diversity, Epidemiology, Genome-Wide Association Studies (GWAS), KCNMB2, FTLD, KATP
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.
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.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.
Audience Academic
Author Nelson, Peter T
Shade, Lincoln M P
Katsumata, Yuriko
Fardo, David W
Author_xml – sequence: 1
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  surname: Katsumata
  fullname: Katsumata, Yuriko
– sequence: 2
  givenname: David W
  surname: Fardo
  fullname: Fardo, David W
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  givenname: Lincoln M P
  surname: Shade
  fullname: Shade, Lincoln M P
– sequence: 5
  givenname: Peter T
  orcidid: 0000-0002-6161-1265
  surname: Nelson
  fullname: Nelson, Peter T
  email: pnels2@email.uky.edu
BackLink https://www.ncbi.nlm.nih.gov/pubmed/37528055$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
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Keene, C Dirk
Buxbaum, Joseph D
Hyman, Bradley T
Duara, Ranjan
Jarvik, Gail P
Albin, Roger L
Green, Robert C
Gearing, Marla
Williamson, Jennifer
Weintraub, Sandra
Karydas, Anna
Burns, Jeffrey M
Lah, James J
Spina, Salvatore
Vonsattel, Jean Paul
Masurkar, Arjun V
DeCarli, Charles
Kaye, Jeffrey A
Smith, Amanda G
Apostolova, Liana G
Larson, Eric B
Vinters, Harry V
Dickson, Dennis W
Barnes, Lisa L
Vassar, Robert
Lopez, Oscar L
Petersen, Ronald C
Quinn, Joseph F
Woltjer, Randall L
Bennett, David A
Brewer, James B
Frosch, Matthew P
Welsh-Bohmer, Kathleen A
Saykin, Andrew J
Troncoso, Juan C
Trojanowski, John Q
Hamilton, Ronald L
Sultzer, David
Miller, Bruce L
Lieberman, Andrew P
Galasko, Douglas R
Mesulam, Marsel
Bowen, James D
Goate, Alison M
Hulette, Christine M
Geschwind, Daniel H
Yu, Lei
Burke, James R
Paulson, Henry L
Wisniewski, Thomas
Lyketsos, Constantine G
McKee, Ann C
Becker, James T
Lawrence, S
Kowall, Neil W
Kamboh, M Ilyas
Parisi, Joseph E
Schneider, Julie A
Harrell, Lindy E
Abner, Erin
Boxer, Adam
McCurry, Susan M
Kim, Ronald
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The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc.
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Keywords KATP
Genome-Wide Association Studies (GWAS)
Epidemiology
Diversity
FTLD
Dementia
KCNMB2
Language English
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Snippet Abstract Limbic-predominant age-related TDP-43 encephalopathy (LATE) affects approximately one-third of older individuals and is associated with cognitive...
Limbic-predominant age-related TDP-43 encephalopathy (LATE) affects approximately one-third of older individuals and is associated with cognitive impairment....
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SourceType Open Access Repository
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Index Database
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Publisher
StartPage 760
SubjectTerms 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
Title LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry
URI https://www.ncbi.nlm.nih.gov/pubmed/37528055
https://www.proquest.com/docview/3051824092
https://www.proquest.com/docview/2845103333
https://pubmed.ncbi.nlm.nih.gov/PMC10440720
Volume 82
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