Alzheimer’s & Dementia | May 25, 2021

Jiang Y, Zhou X, Ip FC, Chan P, Chen Y, Lai NCH, Cheung K, Lo RMN, Tong EPS, Wong BWY, Chan ALT, Mok VCT, Kwok TCY, Mok KY, Hardy J, Zetterberg H, Fu AKY and Ip NY

Alzheimer’s & dementia : the journal of the Alzheimer’s Association. 2021

DOI: https://doi.org/10.1002/alz.12369

Abstract

Introduction

Blood proteins are emerging as candidate biomarkers for Alzheimer’s disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high-performance, blood-based test for AD.

Methods

We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high-throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD.

Results

We identified 429 proteins that were dysregulated in AD plasma. We selected 19 “hub proteins” representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve  = 0.9690–0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage-dependent dysregulation, which can delineate AD stages.

Discussion

This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high-performance, blood-based test for clinical AD screening and staging.