Genetic Insights Into Protective Effects of GLP-1 Receptor Agonists on Stroke and Alzheimer Disease Across Ancestries
Abstract
Background and Objectives: Stroke and dementia are leading causes of death and disability worldwide, requiring enhanced preventive strategies. Glucagon-like peptide-1 receptor agonists (GLP-1RA), widely used for type 2 diabetes (T2D) and obesity, have demonstrated pleiotropic effects, including cardiovascular benefits, with mounting evidence also suggesting potential beneficial effects on brain health. The objective of this study was to investigate the genetically proxied effect of GLP-1RA on stroke, Alzheimer disease (AD), and related endophenotypes, in a cross-ancestry setting. Methods: gene expression. Primary outcomes were stroke (any, ischemic, cardioembolic, small vessel, large artery, and intracerebral hemorrhage) and AD. Secondary analyses included etiologic factors and endophenotypes of stroke and AD: heart failure, atrial fibrillation, MRI markers (white matter hyperintensity volume, perivascular space burden, and hippocampal volume), and CSF biomarkers (beta-amyloid, tau). Outcomes were stratified by ancestry and meta-analyzed. Results: < 0.05), on hippocampal perivascular space burden and CSF β-amyloid levels. Discussion: GLP-1RAs may confer protective effects against stroke (especially ischemic and cardioembolic) and AD risk, across ancestries. These findings warrant further investigation in experimental models and clinical trials to confirm benefits on brain health and understand underlying mechanisms.
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BibTeX
@article{carochatelier2026genetic,
title = {{Genetic Insights Into Protective Effects of GLP-1 Receptor Agonists on Stroke and Alzheimer Disease Across Ancestries}},
author = {Ilana Caro-Châtelier and Muralidharan Sargurupremraj and Chengran Yang and Callistus Akinleye and David-Alexandre Trégouët and Rufus Olusola Akinyemi and Daichi Shigemizu and Motunrayo Coker and Joshua Akinyemi and Hemant Tiwari and Daniel Chasman and Bruce Ovbiagele and Hugues Chabriat and Vincent Mooser and Thierry Couffinhal and Aniket Mishra and Carlos Cruchaga and Christiane Reitz and Brian Kunkle and Yoichiro Kamatani and Mayowa Ojo Owolabi and Kamel Mohammedi and Stéphanie Debette},
journal = {Neurology Genetics},
year = {2026},
month = sep,
doi = {10.1212/nxg.0000000000200425},
url = {https://hal.science/hal-05766858v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Genetic Insights Into Protective Effects of GLP-1 Receptor Agonists on Stroke and Alzheimer Disease Across Ancestries
AU - Ilana Caro-Châtelier
AU - Muralidharan Sargurupremraj
AU - Chengran Yang
AU - Callistus Akinleye
AU - David-Alexandre Trégouët
AU - Rufus Olusola Akinyemi
AU - Daichi Shigemizu
AU - Motunrayo Coker
AU - Joshua Akinyemi
AU - Hemant Tiwari
AU - Daniel Chasman
AU - Bruce Ovbiagele
AU - Hugues Chabriat
AU - Vincent Mooser
AU - Thierry Couffinhal
AU - Aniket Mishra
AU - Carlos Cruchaga
AU - Christiane Reitz
AU - Brian Kunkle
AU - Yoichiro Kamatani
AU - Mayowa Ojo Owolabi
AU - Kamel Mohammedi
AU - Stéphanie Debette
PY - 2026
DA - 2026/09/25
JO - Neurology Genetics
DO - 10.1212/nxg.0000000000200425
UR - https://hal.science/hal-05766858v1
AB - Background and Objectives: Stroke and dementia are leading causes of death and disability worldwide, requiring enhanced preventive strategies. Glucagon-like peptide-1 receptor agonists (GLP-1RA), widely used for type 2 diabetes (T2D) and obesity, have demonstrated pleiotropic effects, including cardiovascular benefits, with mounting evidence also suggesting potential beneficial effects on brain health. The objective of this study was to investigate the genetically proxied effect of GLP-1RA on stroke, Alzheimer disease (AD), and related endophenotypes, in a cross-ancestry setting. Methods: gene expression. Primary outcomes were stroke (any, ischemic, cardioembolic, small vessel, large artery, and intracerebral hemorrhage) and AD. Secondary analyses included etiologic factors and endophenotypes of stroke and AD: heart failure, atrial fibrillation, MRI markers (white matter hyperintensity volume, perivascular space burden, and hippocampal volume), and CSF biomarkers (beta-amyloid, tau). Outcomes were stratified by ancestry and meta-analyzed. Results: < 0.05), on hippocampal perivascular space burden and CSF β-amyloid levels. Discussion: GLP-1RAs may confer protective effects against stroke (especially ischemic and cardioembolic) and AD risk, across ancestries. These findings warrant further investigation in experimental models and clinical trials to confirm benefits on brain health and understand underlying mechanisms.
SN - 2376-7839
ER -