Blood plasma proteomic markers of Alzheimer's disease, current status and application prospects

Expert Rev Proteomics. 2025 Jan 7. doi: 10.1080/14789450.2025.2450804. Online ahead of print.

Abstract

Introduction: Identifying early risks of developing Alzheimer's disease (AD) is a major challenge as the number of patients with AD steadily increases and requires innovative solutions. Current molecular diagnostic modalities, such as cerebrospinal fluid (CSF) testing and positron emission tomography (PET) imaging, exhibit limitations in their applicability for large-scale screening. In recent years, there has been a marked shift toward the development of blood plasma-based diagnostic tests, which offer a more accessible and clinically viable alternative for widespread use. Furthermore, advances in large-scale proteomics technologies have boosted an interest in identifying novel biomarkers and developing panels of AD-associated proteins.

Areas covered: This review mainly examines the results of recent searches for proteomic markers of AD in blood plasma (from 2022-2024 PubMed), focuses on some aspects for special attention in further studies, and discusses the prospects for their further application.

Expert opinion: Recent advances in AD plasma/serum proteomic studies are largely driven using novel Olink/PEA and SomaScan/aptamer technologies, which complement the 'gold standard' of MS-based quantitative proteomics (MRM/SRM), and particularly expand the capabilities for studying low- abundant proteins.

Keywords: Proteomic markers; alzheimer’s disease; blood; mass-spectrometry; plasma.