Early microglial and astrocyte reactivity in preclinical Alzheimer's disease
Introduction: The role of neuroinflammation in preclinical Alzheimer's disease (AD) remains unclear. Methods: We assessed changes in microglial and astrocytic biomarkers in a well-characterized cohort of 211 cognitively unimpaired individuals. Structural equation modeling was used to simultaneously...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2025 |
| Country: | España |
| Institution: | Universidad de Cantabria (UC) |
| Repository: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Language: | English |
| OAI Identifier: | oai:repositorio.unican.es:10902/37729 |
| Online Access: | https://hdl.handle.net/10902/37729 |
| Access Level: | Open access |
| Keyword: | Astrocyte Biomarkers Chitinase-3-like protein 1 (YKL-40) Glial fibrillary acidic protein (GFAP) Microglia Preclinical Alzheimer´s disease S-100 calcium-binding protein beta (S100β) Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) Structural equation modeling |
| Summary: | Introduction: The role of neuroinflammation in preclinical Alzheimer's disease (AD) remains unclear. Methods: We 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. Results: Plasma 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 (Ab42/40. CSF sTREM2 directly influenced CSF phosphorylated tau-181 (p-tau181) and neurogranin, and correlated with CSF S100 calcium-binding protein beta (S100b). CSF chitinase-3-like protein 1 (YKL-40) mediated the association between CSF p-tau181 and total tau (t-tau), whereas CSF S100b 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 S100b contribute to the progression of downstream neurodegenerative changes. |
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