Fluid biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: A systematic review and meta-analysis

Gurpreet Kaur Hansra; Tharusha Jayasena; Satoshi Hosoki; Anne Poljak; Ben Chun Pan Lam; Ruslan Rust; Abhay Sagare; Berislav Zlokovic; Anbupalam Thalamuthu; Perminder S. Sachdev

Cerebral Circulation - Cognition and Behavior (Jan 2024)

Fluid biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: A systematic review and meta-analysis

Gurpreet Kaur Hansra,
Tharusha Jayasena,
Satoshi Hosoki,
Anne Poljak,
Ben Chun Pan Lam,
Ruslan Rust,
Abhay Sagare,
Berislav Zlokovic,
Anbupalam Thalamuthu,
Perminder S. Sachdev

Affiliations

Gurpreet Kaur Hansra: Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, Australia; Corresponding author.
Tharusha Jayasena: Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, Australia
Satoshi Hosoki: Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, Australia; Department of Neurology, National Cerebral and Cardiovascular Centre, Suita, Japan
Anne Poljak: Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, Australia; Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales, NSW, Australia
Ben Chun Pan Lam: Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, Australia
Ruslan Rust: Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Abhay Sagare: Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Berislav Zlokovic: Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Anbupalam Thalamuthu: Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, Australia
Perminder S. Sachdev: Centre for Healthy Brain Ageing, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, Australia

Journal volume & issue: Vol. 6
p. 100216

Abstract

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Background: The disruption of the neurovascular unit (NVU), which maintains the integrity of the blood brain barrier (BBB), has been identified as a critical mechanism in the development of cerebrovascular and neurodegenerative disorders. However, the understanding of the pathophysiological mechanisms linking NVU dysfunction to the disorders is incomplete, and reliable blood biomarkers to measure NVU dysfunction are yet to be established. This systematic review and meta-analysis aimed to identify biomarkers associated with BBB dysfunction in large vessel disease, small vessel disease (SVD) and vascular cognitive disorders (VCD). Methods: A literature search was conducted in PubMed, EMBASE, Scopus and PsychINFO to identify blood biomarkers related to dysfunction of the NVU in disorders with vascular pathologies published until 20 November 2023. Studies that assayed one or more specific markers in human serum or plasma were included. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Effects were pooled and methodological heterogeneity examined using the random effects model. Results: A total of 112 studies were included in this review. Where study numbers allowed, biomarkers were analysed using random effect meta-analysis for VCD (1 biomarker; 5 studies) and cerebrovascular disorders, including stroke and SVD (9 biomarkers; 29 studies) while all remaining biomarkers (n = 17 biomarkers; 78 studies) were examined through qualitative analysis. Results of the meta-analysis revealed that cerebrospinal fluid/serum albumin quotient (Q-Alb) reliably differentiates VCD patients from healthy controls (MD = 2.77; 95 % CI = 1.97–3.57; p < 0.0001) while commonly measured biomarkers of endothelial dysfunction (VEGF, VCAM-1, ICAM-1, vWF and E-selectin) and neuronal injury (NfL) were significantly elevated in vascular pathologies. A qualitative assessment of non-meta-analysed biomarkers revealed NSE, NfL, vWF, ICAM-1, VCAM-1, lipocalin-2, MMP-2 and MMP-9 levels to be upregulated in VCD, although these findings were not consistently replicated. Conclusions: This review identifies several promising biomarkers of NVU dysfunction which require further validation. A panel of biomarkers representing multiple pathophysiological pathways may offer greater discriminative power in distinguishing possible disease mechanisms of VCD.

Published in Cerebral Circulation - Cognition and Behavior

ISSN: 2666-2450 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/cerebral-circulation-cognition-and-behavior

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