Ming Ann Sim, James D. Doecke, Oi Wah Liew, Lee Lee Wong, Eugene S. J. Tan, Siew Pang Chan, Joyce R. F. Chong, Yuan Cai, Saima Hilal, Narayanaswamy Venketasubramanian, Boon Yeow Tan, Alzheimer's Disease Neuroimaging Initiative, Mitchell K. P Lai, Hyungwon Choi, Colin L. Masters, Arthur Mark Richards, Christopher L. H. Chen
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Abstract
INTRODUCTION
The prognostic utility of plasma proteomics for cognitive decline and dementia in a Southeast Asian population characterized by high cerebrovascular disease (CeVD) burden is underexplored.
METHODS
We examined this in a Singaporean memory clinic cohort of 528 subjects (n = 300, CeVD; n = 167, incident cognitive decline) followed-up for 4 years.
RESULTS
Of 1441 plasma proteins surveyed, a 12-protein signature significantly predicted cognitive decline (q-value < .05). Sixteen diverse biological processes were implicated in cognitive decline. Ten proteins independently predicted incident dementia (q-value < .05). A unified prediction model combining plasma proteins with clinical risk factors increased the area under the curve for outcome prediction from 0.62 to 0.85. External validation in the cerebrospinal fluid proteome of an independent Caucasian cohort replicated four of the significantly predictive plasma markers for cognitive decline namely: GFAP, NEFL, AREG, and PPY.
DISCUSSION
The prognostic proteins prioritized in our study provide robust signals in two different biological matrices, representing potential mechanistic targets for dementia and cognitive decline.
Highlights
A total of 1441 plasma proteins were profiled in a Singaporean memory clinic cohort.
We report prognostic plasma protein signatures for cognitive decline and dementia.
External validation was performed in the cerebrospinal fluid proteome of a Caucasian cohort.
A concordant proteomic signature was identified across both biofluids and cohorts.
Further studies are needed to explore the therapeutic implications of these proteins for dementia.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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