title: Identification of a rare coding variant in TREM2 in a Chinese individual with Alzheimer's disease.
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.
authors.affiliation: a Memory and Aging Center, Department of Neurology , University of California, San Francisco , San Francisco , CA , USA.
authors.forename: Luke W
authors.initials: LW
authors.lastname: Bonham
authors.affiliation: b Department of Molecular and Cell Biology, Howard Hughes Medical Institute , University of California, Berkeley , Berkeley , CA , USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Sirkis
authors.affiliation: a Memory and Aging Center, Department of Neurology , University of California, San Francisco , San Francisco , CA , USA.|c Department of Neurology , Second Hospital of Jilin University , Changchun , China.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.affiliation: b Department of Molecular and Cell Biology, Howard Hughes Medical Institute , University of California, Berkeley , Berkeley , CA , USA.
authors.forename: Renan E
authors.initials: RE
authors.lastname: Aparicio
authors.affiliation: a Memory and Aging Center, Department of Neurology , University of California, San Francisco , San Francisco , CA , USA.
authors.forename: Marian
authors.initials: M
authors.lastname: Tse
authors.affiliation: d Department of Psychiatry and Semel Institute for Neuroscience and Human Behavior , The David Geffen School of Medicine at University of California Los Angeles , Los Angeles , CA , USA.
authors.forename: Eliana Marisa
authors.initials: EM
authors.lastname: Ramos
authors.affiliation: d Department of Psychiatry and Semel Institute for Neuroscience and Human Behavior , The David Geffen School of Medicine at University of California Los Angeles , Los Angeles , CA , USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: d Department of Psychiatry and Semel Institute for Neuroscience and Human Behavior , The David Geffen School of Medicine at University of California Los Angeles , Los Angeles , CA , USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: a Memory and Aging Center, Department of Neurology , University of California, San Francisco , San Francisco , CA , USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Rosen
authors.affiliation: a Memory and Aging Center, Department of Neurology , University of California, San Francisco , San Francisco , CA , USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: a Memory and Aging Center, Department of Neurology , University of California, San Francisco , San Francisco , CA , USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Yokoyama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D019921:Biotinylation; D003072:Cognition Disorders / Q000150:complications / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008967:Molecular Biology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human
keywords: Alzheimer’s disease; Chinese; TREM2; case report; dementia; genetics; rare variant