NUS Medicine researchers identify blood proteins that may predict brain and cardiovascular health issues

Researchers from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), have identified four proteins in the blood that could potentially help identify people at higher risk of worsening cerebrovascular disease, cognitive decline, serious heart and stroke-related events, and mortality.

Published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the study analysed more than 1,400 proteins in blood samples spanning two Singapore-based research cohorts. The researchers identified novel blood protein signatures that consistently associated with cerebrovascular disease and poorer health outcomes. Cerebrovascular disease affects the brain’s blood vessels and can cause small areas of tissue injury, microbleeds, and white matter damage, contributing to stroke, cognitive decline, and dementia. The study is the first to track its progression using large-scale protein profiling in a longitudinal Southeast Asian cohort, addressing a gap in research involving Asian populations.

Professor Christopher Chen, Deputy Chair of the Healthy Longevity Translational Research Programme (TRP) at NUS Medicine, who led the study, said, “Cerebrovascular disease is an important contributor to cognitive decline and dementia, particularly in our Asian population. By identifying blood proteins linked to changes in the brain and future cognitive and cardiovascular outcomes, we hope to move towards more precise ways of identifying people at risk and intervening earlier.” Prof Chen is also from the Department of Pharmacology at NUS Medicine, Director, Memory Ageing & Cognition Centre, National University Health System (NUHS), and Senior Consultant, Department of Psychological Medicine, National University Hospital.

The researchers first studied 518 participants from a Singapore memory clinic cohort who underwent blood protein profiling, brain MRI scans, and cognitive assessments. Using an advanced proteomics platform, they measured over 1,400 proteins and mapped them against several lesion types related to cerebrovascular damage such as white matter hyperintensities, lacunes, cerebral microbleeds, and cortical infarcts. Repeat brain imaging over time allowed the team to identify protein patterns associated with both existing disease and its progression, involving processes such as inflammation, immune responses, cell adhesion, and blood clotting. Identified blood protein signatures were further tested in another independent Singaporean cohort, where these proteins were also found to be associated with mortality. The study suggests that blood-based biomarkers could eventually complement brain imaging and clinical risk factors to identify people at greater risk of cerebrovascular disease, cognitive decline, as well as future health, cardiac and cerebrovascular outcomes. Further validation of these early findings is needed before they can be explored within clinical practice.

Dr Sim Ming Ann, first author of the study and PhD student at the Healthy Longevity TRP at NUS Medicine and Memory Ageing & Cognition Centre, NUHS, said, “By studying more than 1,400 proteins simultaneously and mapping them against MRI changes over several years, we gained a broader picture of the biological processes associated with cerebrovascular disease and identified proteins linked to both current disease and future health outcomes.” Dr Sim is also Consultant, Department of Intensive Care Medicine, Ng Teng Fong General Hospital.

Prof Chen added, “Our longer-term goal is to develop more accurate and clinically useful tools that can identify high-risk individuals before substantial brain damage or cognitive decline has occurred. If further validated, blood-based markers could potentially complement existing assessments, and help doctors tailor monitoring and preventive strategies more closely to every individual.”

The team aims to investigate the biological roles of these proteins and their potential use in future treatments or multi-marker tests for earlier and more personalised risk assessment.

This research is supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Pte Ltd under the NMRC Centre Grant (MOH-001014, MOH-001018), Singapore Translational Research Investigator Award (IGMS-MOH-000707) and NMRC Research Training Fellowship (IGMS-MOH-001403), and the National Research Foundation, Singapore (NRF) under the NMRC Open Fund – Large Collaborative Grant (MOH-000500) administered by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd. The research is also supported by the National University Health System (NUHS) Clinician Scientist Academy (NCSP2.0/2023/NUHS/SMA) and National University of Singapore (KCG/2023/NUSMED/SMA).