ArticleMolecular neurodegeneration2019
Early increase of CSF sTREM2 in Alzheimer's disease is associated with tau related-neurodegeneration but not with amyloid-β pathology.
Article in Molecular neurodegeneration, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 1 of them a synthesis that pooled it.
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Who cites it
173 citing papers in PubMed, 1 synthesis or guideline pooled it, 368 citations in OpenAlex.
- Neuroinflammatory fluid biomarkers in patients with Alzheimer's disease: a systematic literature review.Molecular psychiatry · 2025Pooled it
- Inhibition of p38α MAPK increases short-term astrocyte reactivity: the exploratory VIP trial in early Alzheimer's disease.Journal of neuroinflammation · 2025Trial
- Cerebrospinal Fluid Over Plasma Links Analytes to Cognitive Decline in Older Adults at Risk for Alzheimer's Disease.Annals of clinical and translational neurology · 2026Article
- Uncovering the biological mechanisms of TREM2 with molecular simulations: A comprehensive review and perspective.Progress in biophysics and molecular biology · 2026Review
- Soluble TREM2 Mediates Blood Brain Barrier Permeability through Astrocyte Reactivity.Research square · 2026Article
- Neurofilament Light Chain (NfL) in Neurodegenerative Diseases: Biological and Clinical Significance, Multi-Omics Integration, and AI-Driven Biomarker Modeling for Precision Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Review
- APOEε4 attenuates early TREM2-mediated microglial responses and influences disease trajectories in dementia with Lewy bodies.Research square · 2026Article
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Plasma biomarker trajectories across Alzheimer's clinical onset: a 17-year prospective study.Alzheimer's research & therapy · 2026Article
- Mll5 haploinsufficiency attenuates microglial phagocytosis through dysregulated TREM2-SGK3-GSK3β signaling and recapitulates ASD-like behaviors in mice.Nature communications · 2026Article
- Elevated plasma klotho levels attenuate Alzheimer's disease pathologies and cognitive decline in APOE ε4 carriers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Elevated levels of cerebrospinal fluid soluble triggering receptor expressed on myeloid cells 2 in multiple system atrophy: a marker of disease-associated microglial activation.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- A neuroimaging biomarker for disease staging in clinically diagnosed Alzheimer's disease.BMC medicine · 2026Article
- The Immuno-Glial Connectome in Alzheimer's Disease: Integrating Central and Peripheral Inflammatory Networks.Cellular and molecular neurobiology · 2026Review
- Parkinson's disease: spatiotemporal regulation and therapeutic prospects of TREM2-mediated microglial responses.NPJ Parkinson's disease · 2026Review
- Striatal functional connectivity alterations in mild cognitive impairment subtypes defined by CSF A/T biomarkers.Frontiers in aging neuroscience · 2026Article
- Plasma growth-associated protein 43 correlates with synaptic loss in Alzheimer's disease.Cell reports. Medicine · 2025Article
- Leucine-Rich Repeat Kinase 2 Relates to Neuroaxonal Degeneration via Tau Pathology and Microglial Activation in Alzheimer's Disease.Molecular neurobiology · 2025Article
113 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 7 institutions in 4 countries.
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Abstract
backgroundTREM2 is a transmembrane receptor that is predominantly expressed by microglia in the central nervous system. Rare variants in the TREM2 gene increase the risk for late-onset Alzheimer's disease (AD). Soluble TREM2 (sTREM2) resulting from shedding of the TREM2 ectodomain can be detected in the cerebrospinal fluid (CSF) and is a surrogate measure of TREM2-mediated microglia function. CSF sTREM2 has been previously reported to increase at different clinical stages of AD, however, alterations in relation to Amyloid β-peptide (Aβ) deposition or additional pathological processes in the amyloid cascade (such as tau pathology or neurodegeneration) remain unclear. In the current cross-sectional study, we employed the biomarker-based classification framework recently proposed by the NIA-AA consensus guidelines, in combination with clinical staging, in order to examine the CSF sTREM2 alterations at early asymptomatic and symptomatic stages of AD.
methodsA cross-sectional study of 1027 participants of the Alzheimer's Disease Imaging Initiative (ADNI) cohort, including 43 subjects carrying TREM2 rare genetic variants, was conducted to measure CSF sTREM2 using a previously validated enzyme-linked immunosorbent assay (ELISA). ADNI participants were classified following the A/T/N framework, which we implemented based on the CSF levels of Aβ
resultsCSF sTREM2 differed between TREM2 variants, whereas the p.R47H variant had higher CSF sTREM2, p.L211P had lower CSF sTREM2 than non-carriers. We found that CSF sTREM2 increased in early symptomatic stages of late-onset AD but, unexpectedly, we observed decreased CSF sTREM2 levels at the earliest asymptomatic phase when only abnormal Aβ pathology (A+) but no tau pathology or neurodegeneration (TN-), is present.
conclusionsAβ pathology (A) and tau pathology/neurodegeneration (TN) have differing associations with CSF sTREM2. While tau-related neurodegeneration is associated with an increase in CSF sTREM2, Aβ pathology in the absence of downstream tau-related neurodegeneration is associated with a decrease in CSF sTREM2.
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