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Alzheimer's & dementia : the journal of the Alzheimer's Association
Published

Blood biomarkers of vascular dysfunction in small vessel disease progression: Insights from a longitudinal neuroimaging study

Authors

Daniela Jaime Garcia, Una Clancy, Carmen Arteaga, Maria C Valdés-Hernandez, Francesca M Chappell, Angela C C Jochems, Yajun Cheng, Junfang Zhang, Michael J Thrippleton, Michael S Stringer, Emilie Sleight, Ellen V Backhouse, Stewart Wiseman, Rosalind Brown, Fergus N Doubal, Axel Montagne, Joanna M Wardlaw, MSS3 Study Group

Abstract

Alzheimers Dement. 2025 Apr;21(4):e70152. doi: 10.1002/alz.70152.

ABSTRACT

INTRODUCTION: This study explored the relationship between blood biomarkers of cerebrovascular function and small vessel disease (SVD) neuroimaging markers and cognitive outcomes in highly-phenotyped participants.

METHODS: We conducted cross-sectional and 1-year longitudinal analyses on 181 patients with mild ischemic stroke, enriched for SVD features. We examined relationships between a panel of 13 blood biomarkers and magnetic resonance imaging (MRI) markers of SVD (structural lesions, diffusion-weighted imaging [DWI]-positive lesions, blood-brain barrier (BBB) permeability, and cerebrovascular reactivity (CVR), and cognition.

RESULTS: In linear mixed models, vascular endothelial growth factor was significantly associated with incident DWI-positive lesions over 1 year. Intercellular adhesion molecule-1 was linked with lower CVR while platelet-derived growth factor-subunit B and Endothelin-1 were associated with higher CVR. Platelet-Selectin levels were associated with mild cognitive impairment at 1 year.

DISCUSSION: Our results support the role of endothelial and pericyte dysfunction in SVD burden and progression and suggest that specific biomarkers relate to distinct SVD manifestations.

HIGHLIGHTS: Small vessel disease (SVD) lacks specific or predictive biomarker signatures. Vascular endothelial growth factor levels were linked to incident lesions detected over 1 year. Circulating intercellular adhesion molecule-1 related to lower cerebrovascular reactivity. Platelet-selectin levels were associated with mild cognitive impairment longitudinally. These findings could help stratify patients at high-risk of rapid-progression SVD.

PMID:40275856 | DOI:10.1002/alz.70152

UK DRI Authors

Axel Montagne

Dr Axel Montagne

Group Leader

Exploring the link between cerebrovascular and inflamm-ageing to neurodegeneration and dementia

Dr Axel Montagne