Rare TREM2 variants associated with Alzheimer's disease display reduced cell surface expression
| Autor: | Sirkis, Daniel W, Bonham, Luke W, Aparicio, Renan E, Geier, Ethan G, Ramos, Eliana Marisa, Wang, Qing, Karydas, Anna, Miller, Zachary A, Miller, Bruce L, Coppola, Giovanni, Yokoyama, Jennifer S |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Aging Clinical Sciences Nasu-Hakola disease Neurodegenerative Cohort Studies Alzheimer Disease Immunologic Receptors Acquired Cognitive Impairment TREM2 Genetics Humans 2.1 Biological and endogenous factors Alzheimer's Disease including Alzheimer's Disease Related Dementias Genetic Predisposition to Disease Polymorphism Aetiology Aged Membrane Glycoproteins Cell Membrane Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Single Nucleotide Alzheimer's disease Brain Disorders HEK293 Cells Case-Control Studies Neurological Female Dementia Biochemistry and Cell Biology Alzheimer’s disease |
| Zdroj: | Sirkis, DW; Bonham, LW; Aparicio, RE; Geier, EG; Ramos, EM; Wang, Q; et al.(2016). Rare TREM2 variants associated with Alzheimer's disease display reduced cell surface expression. ACTA NEUROPATHOLOGICA COMMUNICATIONS, 4, 98. doi: 10.1186/s40478-016-0367-7. UCLA: Retrieved from: http://www.escholarship.org/uc/item/9rk6d6m3 Acta neuropathologica communications, vol 4, iss 1 |
| DOI: | 10.1186/s40478-016-0367-7. |
| Popis: | Rare variation in TREM2 has been associated with greater risk for Alzheimer's disease (AD). TREM2 encodes a cell surface receptor expressed on microglia and related cells, and the R47H variant associated with AD appears to affect the ability of TREM2 to bind extracellular ligands. In addition, other rare TREM2 mutations causing early-onset neurodegeneration are thought to impair cell surface expression. Using a sequence kernel association (SKAT) analysis in two independent AD cohorts, we found significant enrichment of rare TREM2 variants not previously characterized at the protein level. Heterologous expression of the identified variants showed that novel variants S31F and R47C displayed significantly reduced cell surface expression. In addition, we identified rare variant R136Q in a patient with language-predominant AD that also showed impaired surface expression. The results suggest rare TREM2 variants enriched in AD may be associated with altered TREM2 function and that AD risk may be conferred, in part, from altered TREM2 surface expression. |
| Databáze: | OpenAIRE |
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