In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 11, No. 507 ( 2019-08-28)
Abstract:
Loss of function of TREM2, a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer’s disease (AD). We therefore examined whether soluble TREM2 (sTREM2) concentrations in cerebrospinal fluid (CSF) were associated with reduced rates of cognitive decline and clinical progression in subjects with AD or mild cognitive impairment (MCI). We measured sTREM2 in CSF samples from 385 elderly subjects, including cognitively normal controls, individuals with MCI, and subjects with AD dementia (follow-up period: mean, 4 years; range 1.5 to 11.5 years). In subjects with AD defined by evidence of CSF Aβ 1–42 (amyloid β-peptide 1 to 42; A+) and CSF p-tau 181 (tau phosphorylated on amino acid residue 181; T+), higher sTREM2 concentrations in CSF at baseline were associated with attenuated decline in memory and cognition. When analyzed in clinical subgroups, an association between higher CSF sTREM2 concentrations and subsequent reduced memory decline was consistently observed in individuals with MCI or AD dementia, who were positive for CSF Aβ 1–42 and CSF p-tau 181 (A+T+). Regarding clinical progression, a higher ratio of CSF sTREM2 to CSF p-tau 181 concentrations predicted slower conversion from cognitively normal to symptomatic stages or from MCI to AD dementia in the subjects who were positive for CSF Aβ 1–42 and CSF p-tau 181. These results suggest that sTREM2 is associated with attenuated cognitive and clinical decline, a finding with important implications for future clinical trials targeting the innate immune response in AD.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.aav6221
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2019
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