ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Early microglial and astrocyte reactivity in preclinical Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association of Alzheimer's disease progression with YKL40 levels in peripheral blood and cerebrospinal fluid: a systematic review and meta-analysis.Frontiers in neurologyPooled it
- Neuroinflammation and Tauopathies.Molecular biology reports · 2026Review
- Early microglial response to amyloid plaques drives sleep loss in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Glial fibrillary acidic protein (GFAP) in biofluids: analytical considerations and clinical relevance in neurodegenerative diseases.Journal of neurology · 2026Review
- How does type 2 diabetes modify the risk of Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- BAG3 modulates clathrin-mediated endocytosis and tau uptake in astrocytes.American journal of physiology. Cell physiology · 2026Article
- Diagnostic performance of plasma GFAP in preclinical stages of Alzheimer's disease using the Lumipulse platform.Alzheimer's research & therapy · 2026Article
- Review
- TREM2 as a central immunometabolic hub in Alzheimer's disease: linking microglial states, lipid stress, and disease-stage-specific intervention.Frontiers in immunology · 2026Review
- Neuronal PARIS-STAT3 axis drives tau pathology and glial activation in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- The Biomarker Profile of Alzheimer's Disease for Disease-Modifying Treatment Eligibility: Questions and Debates.International journal of molecular sciences · 2025Review
- Early microglial and astrocyte reactivity in preclinical Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Alzheimer's disease heterogeneity and co-pathologies: Defining novel targets, biomarkers, modalities, and research methodologies.Alzheimer's & dementia (New York, N. Y.)Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
introductionThe role of neuroinflammation in preclinical Alzheimer's disease (AD) remains unclear.
methodsWe assessed changes in microglial and astrocytic biomarkers in a well-characterized cohort of 211 cognitively unimpaired individuals. Structural equation modeling was used to simultaneously assess all relationships among microglial and astrocytic responses and AD pathological events.
resultsPlasma glial fibrillary acidic protein (GFAP) and cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cells 2 (sTREM2) were increased in preclinical AD. Plasma GFAP showed an inverse bidirectional relationship with CSF amyloid beta (Aβ)42/40. CSF sTREM2 directly influenced CSF phosphorylated tau-181 (p-tau181) and neurogranin, and correlated with CSF S100 calcium-binding protein beta (S100β). CSF chitinase-3-like protein 1 (YKL-40) mediated the association between CSF p-tau181 and total tau (t-tau), whereas CSF S100β and neurofilament light showed mutual influence. DISCUSSION: Our findings suggest that microglial and astrocyte reactivity, measured through fluid biomarkers, occur early and impact the amyloid cascade on the preclinical Alzheimer´s continuum. Specifically, GFAP influences amyloid accumulation, sTREM2 promotes tau pathology, and YKL-40 and S100β contribute to the progression of downstream neurodegenerative changes. HIGHLIGHTS: Preclinical Alzheimer's disease (AD) showed increased levels of plasma glial fibrillary acidic protein (GFAP) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) compared to cerebrospinal fluid (CSF) in healthy subjects. Higher plasma GFAP levels was directly associated with lower CSF amyloid beta (Aβ)42/Aβ40. Higher CSF sTREM2 concentrations increased CSF phosphorylated tau-181. Chitinase-3-like protein 1 (YKL-40) mediated tau-induced neurodegeneration. S100 calcium-binding protein beta (S100β) was directly linked to higher neurofilament light (NfL) and showed a mutual relationship with sTREM2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.