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Proteomics as a reliable approach for discovery of blood-based Alzheimer's disease biomarkers: a systematic review and meta-analysis.

Siti Hajar Rehiman,S. Lim,C. Neoh,A. Majeed,A. Chin,M. Tan,S. Kamaruzzaman,K. Ramasamy

Published 2020 in Ageing Research Reviews

ABSTRACT

In order to gauge the impact of proteomics in discovery of Alzheimer's disease (AD) blood-based biomarkers, this study had systematically reviewed articles published between 1984-2019. Articles that fulfilled the inclusion criteria were assessed for risk of bias. A meta-analysis was performed for replicable candidate biomarkers (CB). Of the 1,651 articles that were identified, 17 case-control and two cohort studies, as well as three combined case-control and longitudinal designs were shortlisted. A total of 207 AD and mild cognitive impairment (MCI) CB were discovered, with 48 reported in >2 studies. This review highlights six CB, namely alpha-2-macroglobulin (α2 M)ps, pancreatic polypeptide (PP)ps, apolipoprotein A-1 (ApoA-1)ps, afaminp, insulin growth factor binding protein-2 (IGFBP-2)ps and fibrinogen-γ-chainp, all of which exhibited consistent pattern of regulation in >three independent cohorts. They are involved in AD pathogenesis via amyloid-beta (Aβ), neurofibrillary tangles, diabetes and cardiovascular diseases (CVD). Meta-analysis indicated that ApoA-1ps was significantly downregulated in AD (SMD=-1.52, 95% CI: -1.89, -1.16, p < 0.00001), with low inter-study heterogeneity (I2 = 0%, p = 0.59). α2Mps was significantly upregulated in AD (SMD = 0.83, 95% CI: 0.05, 1.62, p = 0.04), with moderate inter-study heterogeneity (I2 = 41%, p = 0.19). Both CB are involved in Aβ formation. These findings provide important insights into blood-based AD biomarkers discovery via proteomics.

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