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

Warmenhoven, Noëlle LU orcid ; Sánchez-Benavides, Gonzalo ; González-Escalante, Armand ; Milà-Alomà, Marta ; Shekari, Mahnaz ; López-Martos, David ; Ortiz-Romero, Paula ; Kollmorgen, Gwendlyn ; Quijano-Rubio, Clara and Minguillón, Carolina , et al. (2024) In Alzheimer's and Dementia 20(9). p.5819-5832
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)... (More)

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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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, chitinase 3-like protein 1, cognition, cognitively unimpaired, glial biomarkers, glial fibrillary acidic protein, preclinical, soluble triggering receptor expressed on myeloid cell 2
in
Alzheimer's and Dementia
volume
20
issue
9
pages
14 pages
publisher
Wiley
external identifiers
  • scopus:85199007747
  • pmid:39032119
ISSN
1552-5260
DOI
10.1002/alz.13862
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
id
d6bb6998-1710-489a-b1d8-1c59d2d76333
date added to LUP
2024-11-27 10:50:13
date last changed
2025-07-10 05:33:24
@article{d6bb6998-1710-489a-b1d8-1c59d2d76333,
  abstract     = {{<p>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.</p>}},
  author       = {{Warmenhoven, Noëlle and Sánchez-Benavides, Gonzalo and González-Escalante, Armand and Milà-Alomà, Marta and Shekari, Mahnaz and López-Martos, David and Ortiz-Romero, Paula and Kollmorgen, Gwendlyn and Quijano-Rubio, Clara and Minguillón, Carolina and Gispert, Juan Domingo and Vilor-Tejedor, Natalia and Arenaza-Urquijo, Eider and Palpatzis, Eleni and Ashton, Nicholas J. and Zetterberg, Henrik and Blennow, Kaj and Suárez-Calvet, Marc and Grau-Rivera, Oriol}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's disease; chitinase 3-like protein 1; cognition; cognitively unimpaired; glial biomarkers; glial fibrillary acidic protein; preclinical; soluble triggering receptor expressed on myeloid cell 2}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{5819--5832}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1002/alz.13862}},
  doi          = {{10.1002/alz.13862}},
  volume       = {{20}},
  year         = {{2024}},
}