@article{10902/37729,
year = {2025},
url = {https://hdl.handle.net/10902/37729},
abstract = {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.},
publisher = {Wiley},
publisher = {Alzheimer's & Dementia: the Journal of the Alzheimer's Association, 2025, 21, e70502},
title = {Early microglial and astrocyte reactivity in preclinical Alzheimer's disease},
author = {Fernández-Matarrubia, Marta and Valera-Barrero, Andrea and Renuncio-García, Mónica and Aguilella, Marcos and Lage, Carmen and López-García, Sara and Ocejo-Vinyals, J. Gonzalo and Martínez-Dubarbie, Francisco and Corrales-Pardo, Andrea and Bravo González, María Paz and López Hoyos, Marcos and Irure-Ventura, Juan and Blennow, Kaj and Ashton, Nicholas J. and Zetterberg, Henrik and Sánchez-Juan, Pascual and Rodríguez Rodríguez, Eloy Manuel},
}