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 simultaneo...

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Detalles Bibliográficos
Autores: Fernández-Matarrubia, Marta, Valera-Barrero, Andrea, Renuncio-García, Mónica, Aguilella, Marcos, Lage, Carmen, López-García, Sara, Ocejo-Vinyals, Javier Gonzalo, Martínez-Dubarbie, Francisco, Corrales-Pardo, Andrea, Bravo González, María Paz, López Hoyos, Marcos, Irure-Ventura, Juan, Blennow, Kaj, Ashton, Nicholas J., Zetterberg, Henrik, Sánchez-Juan, Pascual|||0000-0002-6081-8037, Rodríguez Rodríguez, Eloy Manuel
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/37729
Acceso en línea:https://hdl.handle.net/10902/37729
Access Level:acceso abierto
Palabra clave: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
Descripción
Sumario: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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