CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease

Warmenhoven, Noëlle; Sánchez Benavides, Gonzalo; González Escalante, Armand; Milà Alomà, Marta; Shekari, Mahnaz; López Martos, David; Ortiz Romero, Paula, 1994-; Kollmorgen, Gwendlyn; Quijano Rubio, Clara; Minguillón, Carolina; Gispert López, Juan Domingo; Vilor Tejedor, Natàlia, 1988-; Arenaza Urquijo, Eider M.; Palpatzis, Eleni; Ashton, Nicholas J.; Zetterberg, Henrik; Blennow, Kaj; Suárez-Calvet, Marc; Grau-Rivera, Oriol; ALFA Study

doi:http://dx.doi.org/10.1002/alz.13862

CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease

Citation

Warmenhoven 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.13862

Abstract

Introduction: 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.