Title | Identification of a rare coding variant in TREM2 in a Chinese individual with Alzheimer's disease. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Bonham LW, Sirkis DW, Fan J, Aparicio RE, Tse M, Ramos EMarisa, Wang Q, Coppola G, Rosen HJ, Miller BL, Yokoyama JS |
Journal | Neurocase |
Volume | 23 |
Issue | 1 |
Pagination | 65-69 |
Date Published | 2017 Feb |
ISSN | 1465-3656 |
Keywords | Aged, Aged, 80 and over, Alzheimer Disease, Asian Continental Ancestry Group, Biotinylation, Cognition Disorders, Cohort Studies, Female, HEK293 Cells, Humans, Male, Membrane Glycoproteins, Molecular Biology, Polymorphism, Single Nucleotide, Receptors, Immunologic, Transfection |
Abstract | Rare variation in the TREM2 gene is associated with a broad spectrum of neurodegenerative disorders including Alzheimer's disease (AD). TREM2 encodes a receptor expressed in microglia which is thought to influence neurodegeneration by sensing damage signals and regulating neuroinflammation. Many of the variants reported to be associated with AD, including the rare R47H variant, were discovered in populations of European ancestry and have not replicated in diverse populations from other genetic backgrounds. We utilized a cohort of elderly Chinese individuals diagnosed as cognitively normal, or with mild cognitive impairment or AD to identify a rare variant, A192T, present in a single patient diagnosed with AD. We characterized this variant using biochemical cell surface expression assays and found that it significantly altered cell surface expression of the TREM2 protein. Together these data provide evidence that the A192T variant in TREM2 could contribute risk for AD. This study underscores the increasingly recognized role of immune-related processes in AD and highlights the importance of including diverse populations in research to identify genetic variation that contributes risk for AD and other neurodegenerative disorders. |
DOI | 10.1080/13554794.2017.1294182 |
Alternate Journal | Neurocase |
PubMed ID | 28376694 |
PubMed Central ID | PMC5639900 |
Grant List | F32 AG050404 / AG / NIA NIH HHS / United States K01 AG049152 / AG / NIA NIH HHS / United States K24 AG045333 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States |
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