| Title: |
LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry. |
| Authors: |
Katsumata, Yuriko; Fardo, David W; Shade, Lincoln MP; Bowen, James D; Crane, Paul K; Jarvik, Gail P; Keene, C Dirk; Larson, Eric B; McCormick, Wayne C; McCurry, Susan M; Mukherjee, Shubhabrata; Kowall, Neil W; McKee, Ann C; Honig, Robert A; Lawrence, S; Vonsattel, Jean Paul; Williamson, Jennifer; Small, Scott; Burke, James R; Hulette, Christine M; Welsh-Bohmer, Kathleen A; Gearing, Marla; Lah, James J; Levey, Allan I; Wingo, Thomas S; Apostolova, Liana G; Farlow, Martin R; Ghetti, Bernardino; Saykin, Andrew J; Spina, Salvatore; Albert, Marilyn S; Lyketsos, Constantine G; Troncoso, Juan C; Frosch, Matthew P; Green, Robert C; Growdon, John H; Hyman, Bradley T; Tanzi, Rudolph E; Potter, Huntington; Dickson, Dennis W; Ertekin-Taner, Nilufer; Graff-Radford, Neill R; Parisi, Joseph E; Petersen, Ronald C; Duara, Ranjan; Buxbaum, Joseph D; Goate, Alison M; Sano, Mary; Masurkar, Arjun V; Wisniewski, Thomas; Bigio, Eileen H; Mesulam, Marsel; Weintraub, Sandra; Vassar, Robert; Kaye, Jeffrey A; Quinn, Joseph F; Woltjer, Randall L; Barnes, Lisa L; Bennett, David A; Schneider, Julie A; Yu, Lei; Henderson, Victor; Fallon, Kenneth B; Harrell, Lindy E; Marson, Daniel C; Roberson, Erik D; DeCarli, Charles; Jin, Lee-Way; Olichney, John M; Kim, Ronald; LaFerla, Frank M; Monuki, Edwin; Head, Elizabeth; Sultzer, David; Geschwind, Daniel H; Vinters, Harry V; Chesselet, Marie-Francoise; Galasko, Douglas R; Brewer, James B; Boxer, Adam; Karydas, Anna; Kramer, Joel H; Miller, Bruce L; Rosen, Howard J; Seeley, William W; Burns, Jeffrey M; Swerdlow, Russell H; Abner, Erin; Van Eldik, Linda J; Albin, Roger L; Lieberman, Andrew P; Paulson, Henry L; Arnold, Steven E; Trojanowski, John Q; Van Deerlin, Vivianna M; Hamilton, Ronald L; Kamboh, M Ilyas; Lopez, Oscar L; Becker, James T |
| Source: |
Journal of Neuropathology & Experimental Neurology, vol 82, iss 9 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2023 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3209 Neurosciences (for-2020); 3202 Clinical Sciences (for-2020); Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) (rcdc); Prevention (rcdc); Aging (rcdc); Alzheimer's Disease (rcdc); Human Genome (rcdc); Acquired Cognitive Impairment (rcdc); Brain Disorders (rcdc); Neurodegenerative (rcdc); Health Disparities and Racial or Ethnic Minority Health Research (rcdc); Neurosciences (rcdc); Genetics (rcdc); Dementia (rcdc); Minority Health (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); TDP-43 Proteinopathies (mesh); Aging (mesh); Alzheimer Disease (mesh); Nerve Tissue Proteins (mesh); Dementia (mesh); Sulfonylurea Receptors (mesh); Polymorphism; Single Nucleotide (mesh); Alleles (mesh); Membrane Proteins (mesh); Progranulins (mesh); Humans (mesh); Alzheimer’s Disease Genetics Consortium |
| Subject Geographic: |
760 - 768 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt6mt3x8tr; https://escholarship.org/uc/item/6mt3x8tr; https://escholarship.org/content/qt6mt3x8tr/qt6mt3x8tr.pdf |
| DOI: |
10.1093/jnen/nlad059 |
| Availability: |
https://escholarship.org/uc/item/6mt3x8tr; https://escholarship.org/content/qt6mt3x8tr/qt6mt3x8tr.pdf; https://doi.org/10.1093/jnen/nlad059 |
| Rights: |
CC-BY-NC |
| Accession Number: |
edsbas.8CAC0C04 |
| Database: |
BASE |