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Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer's disease
- Source :
- Sci Transl Med, Science Translational Medicine, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, Science translational medicine 11(507), eaav6221 (2019). doi:10.1126/scitranslmed.aav6221, Science translational medicine, vol 11, iss 507
- Publication Year :
- 2018
-
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 A beta(1-42) (amyloid beta-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 A beta(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 A beta(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.
- Subjects :
- Aging
cerebrospinal fluid [Amyloid beta-Peptides]
Neurodegenerative
physiology [Receptors, Immunologic]
Neuropsychological Tests
Alzheimer's Disease
Medical and Health Sciences
physiology [Membrane Glycoproteins]
Cerebrospinal fluid
Cognition
Immunologic
Receptors
2.1 Biological and endogenous factors
Aetiology
Cognitive decline
Receptors, Immunologic
Receptor
Membrane Glycoproteins
Microglia
physiology [Cognition]
General Medicine
Biological Sciences
cerebrospinal fluid [Alzheimer Disease]
medicine.anatomical_structure
Neurological
ddc:500
cerebrospinal fluid [Membrane Glycoproteins]
Alzheimer's Disease Neuroimaging Initiative
medicine.medical_specialty
Amyloid
tau Proteins
physiopathology [Alzheimer Disease]
Article
Clinical Research
Alzheimer Disease
Internal medicine
mental disorders
Acquired Cognitive Impairment
medicine
Dementia
Humans
Amyloid beta-Peptides
business.industry
TREM2
Neurosciences
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Alzheimer’s Disease Neuroimaging Initiative
medicine.disease
Brain Disorders
Endocrinology
Cross-Sectional Studies
cerebrospinal fluid [tau Proteins]
business
Subjects
Details
- ISSN :
- 19466242 and 19466234
- Volume :
- 11
- Issue :
- 507
- Database :
- OpenAIRE
- Journal :
- Science translational medicine
- Accession number :
- edsair.doi.dedup.....4b05ea658b16eebf8e138c3ad8817ab9