Warmenhoven, NoëlleSánchez Benavides, GonzaloGonzález Escalante, ArmandMilà Alomà, MartaShekari, MahnazLópez Martos, DavidOrtiz Romero, Paula, 1994-Kollmorgen, GwendlynQuijano Rubio, ClaraMinguillón, CarolinaGispert López, Juan DomingoVilor Tejedor, Natàlia, 1988-Arenaza Urquijo, Eider M.Palpatzis, EleniAshton, Nicholas J.Zetterberg, HenrikBlennow, KajSuárez-Calvet, MarcGrau-Rivera, OriolALFA Study2024-09-232024-09-232024Warmenhoven N, Sánchez-Benavides G, González-Escalante A, Milà-Alomà M, Shekari M, López-Martos D, et al. CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease. Alzheimers Dement. 2024 Sep;20(9):5819-32. DOI: 10.1002/alz.138621552-5260http://hdl.handle.net/10230/61197Introduction: We examined whether baseline glial markers soluble triggering receptor expressed on myeloid cell 2 (sTREM2), chitinase 3-like protein 1 (YKL-40), and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF), and plasma GFAP are associated with cognitive change in cognitively unimpaired (CU) individuals at risk of Alzheimer's disease (AD). Methods: A total of 353 CU (mean age 60.9 years) participants were included (mean follow-up time 3.28 years). Linear regression models with cognition as outcome were used. We also tested whether amyloid beta (Aβ) status modified these associations. Results: Higher baseline CSF sTREM2 was associated with a positive global cognition (Preclinical Alzheimer's Cognitive Composite) rate of change, and better memory and executive outcomes, independently of AD pathology. Higher baseline plasma GFAP was associated with a decline on attention rate of change. Stratified analyses by Aβ status showed that CSF sTREM2 and YKL-40 were positively associated with executive functioning in amyloid negative (Aβ-) individuals. Discussion: Our results suggest that a TREM2-mediated microglial response may be associated with better longitudinal cognitive performance. Highlights: Higher cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cell 2 (sTREM2) relates to better longitudinal cognitive performance. The association between CSF sTREM2 and cognition is independent of Alzheimer's disease (AD) pathology. Targeting microglial reactivity may be a therapeutic strategy for AD prevention.application/pdfeng© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1002/alz.13862Alzheimer's diseaseChitinase 3‐like protein 1CognitionCognitively unimpairedGlial biomarkersGlial fibrillary acidic proteinPreclinicalSoluble triggering receptor expressed on myeloid cell 2info:eu-repo/semantics/openAccess