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.
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This post is Copyright: Noëlle Warmenhoven,
Gonzalo Sánchez‐Benavides,
Armand González‐Escalante,
Marta Milà‐Alomà,
Mahnaz Shekari,
David López‐Martos,
Paula Ortiz‐Romero,
Gwendlyn Kollmorgen,
Clara Quijano‐Rubio,
Carolina Minguillón,
Juan Domingo Gispert,
Natalia Vilor‐Tejedor,
Eider Arenaza‐Urquijo,
Eleni Palpatzis,
Nicholas J Ashton,
Henrik Zetterberg,
Kaj Blennow,
Marc Suárez‐Calvet,
Oriol Grau‐Rivera,
for the ALFA Study | July 20, 2024