期刊
NEUROBIOLOGY OF AGING
卷 74, 期 -, 页码 182-190出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2018.10.022
关键词
Alzheimer's disease; Dementia; Mild cognitive impairment; Biomarker; Neuroinflammation; Neurodegeneration; Imaging; Prediction
资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Abbott
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Amorfix Life Sciences Ltd
- AstraZeneca
- Bayer HealthCare
- BioClinica, Inc
- Biogen Idec Inc
- BristolMyers Squibb Company
- Eisai Inc
- Elan Pharmaceuticals Inc
- Eli Lilly and Company
- F. Hoffmann-La Roche Ltd
- Genentech, Inc
- GE Healthcare
- Innogenetics, N.V.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Medpace, Inc
- Merck Co, Inc
- Meso Scale Diagnostics, LLC.
- Novartis Pharmaceuticals Corporation
- Pfizer Inc
- Servier
- Synarc Inc
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- NIH [P30 AG010129, K01 AG030514]
TREM2 was suggested to be an important regulator of microglia during neurodegeneration, but previous studies report conflicting results in relation to soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF) when using clinical criteria to classify Alzheimer's disease (AD). The present study explores sTREM2 CSF levels and their associations with other biomarkers and cognitive measures in a prospective AD cohort. Based on the available CSF biomarker information, 497 subjects were classified according to the 2018 National Institute on Aging-Alzheimer's Association research framework guidelines, which group biomarkers into those of amyloid-beta deposition, tau pathology, and neurodegeneration. CSF sTREM2 concentrations were associated with markers of neurodegeneration and fibrillar tau pathology, but not amyloidosis; sTREM2 concentrations were increased in total tau-positive versus -negative individuals; sTREM2 was not related to cognitive and other biomarker changes over time; and sTREM2 concentrations increased over time in total tau-positive versus -negative individuals with AD pathophysiology. The present study provides evidence in support of sTREM2 in CSF as a marker of neuroinflammation across the spectrum of early clinical AD. sTREM2 is linked to neuronal injury and may therefore offer complementary information relevant for diagnostic purposes and novel treatment approaches targeting the immune system in AD. (C) 2018 Elsevier Inc. All rights reserved.
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