Preprint Article Version 1 This version is not peer-reviewed

Blood-Brain Barrier Integrity Disruption is Associated to both Chronic Vascular Risk Factors and White Matter Hyperintensities

James Xiao Yuan Chen
ORCID logo ,
Ashwati Vipin
,
Gurveen Kaur Sandhu
,
Yi Jin Leow
ORCID logo ,
Fatin Zahra Zailan
,
Pricilia Tanoto
,
Ee Soo Lee
,
Khang Leng Lee
,
Christine Cheung
ORCID logo ,
Negaenderan Kandiah
*
Version 1 : Received: 24 September 2024 / Approved: 24 September 2024 / Online: 25 September 2024 (08:26:47 CEST)

How to cite: Chen, J. X. Y.; Vipin, A.; Sandhu, G. K.; Leow, Y. J.; Zailan, F. Z.; Tanoto, P.; Lee, E. S.; Lee, K. L.; Cheung, C.; Kandiah, N. Blood-Brain Barrier Integrity Disruption is Associated to both Chronic Vascular Risk Factors and White Matter Hyperintensities. Preprints 2024, 2024091943. https://doi.org/10.20944/preprints202409.1943.v1 Chen, J. X. Y.; Vipin, A.; Sandhu, G. K.; Leow, Y. J.; Zailan, F. Z.; Tanoto, P.; Lee, E. S.; Lee, K. L.; Cheung, C.; Kandiah, N. Blood-Brain Barrier Integrity Disruption is Associated to both Chronic Vascular Risk Factors and White Matter Hyperintensities. Preprints 2024, 2024091943. https://doi.org/10.20944/preprints202409.1943.v1

Abstract

Cardiovascular risk factors (CRFs) such as hypertension, high cholesterol, and diabetes are increasingly implicated in cognitive decline and cerebral small vessel disease (cSVD). White matter hyperintensities (WMH), a hallmark of cSVD, are strongly linked to cognitive impairment, but their underlying mechanisms remain unclear. Blood-brain barrier (BBB) dysfunction has been proposed as a potential contributor to WMH development. This study aimed to explore the relationships between CRFs, BBB integrity, and WMH burden. We analyzed 155 participants from the Biomarkers and Cognition Study, Singapore, assessing CRFs through blood tests for glucose and lipid profiles, alongside blood pressure measurements. WMH volume was quantified using MRI, and an in vitro assay evaluated the impact of plasma on BBB integrity using human brain microvascular endothelial cells. Results showed that plasma from participants with higher WMH burden correlated with increased BBB disruption, which was further associated with higher blood pressure, elevated blood glucose, and lipid levels. Both periventricular and subcortical WMH were linked to BBB disruption. These findings suggest that CRFs contribute to BBB dysfunction, promoting WMH development and cognitive decline in cSVD. Further research is needed to clarify the precise mechanisms driving these associations.

Keywords

cerebral small vessel disease; blood-brain barrier; cardiovascular risk factors; white matter hyperintensity; transendothelial electrical resistance assay

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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