Amyloid‐β sequester proteins as blood‐based biomarkers of cognitive decline

Abstract

Introduction There are no blood-based biomarkers for cognitive decline in aging, or mild cognitive impairment (MCI) and Alzheimer's disease (AD). Cumulative evidence suggests that apolipoproteins, complement system, and transthyretin are involved in AD pathogenesis by sequestration of amyloid β. However, there is no clinical study to assess the utility of “sequester proteins” in risk assessment and/or diagnosis of MCI and AD. Methods Serum levels of sequester proteins and their clinical potential in cognitive decline assessment were analyzed by longitudinal and cross-sectional studies using independent cohorts and were confirmed by a prospective study. Results A combination of apolipoprotein A1, complement C3, and transthyretin achieved an area under the curve of 0.89 (sensitivity 91% and specificity 80%) in MCI versus healthy controls and also discriminated individuals with mild cognitive decline from healthy controls. Discussion A set of sequester proteins could be blood-based biomarkers for assessment of early stages of cognitive decline.

Effect of Anserine/Carnosine Supplementation on Verbal Episodic Memory in Elderly People

“…The cognitive and psychological tests were performed under double-blind conditions. A Mini-Mental State Examination (MMSE) was also conducted, to assess baseline cognitive function [ 22 ].…”

Blood-based molecular biomarkers for Alzheimer’s disease

“…Soares et al, after failing to replicate efficacy in the Ray panel, proposed an alternative 89-analyte panel with a diagnostic accuracy of 70% [26]. Subsequently, there have been numerous contributions of multivariate signatures for differentiating AD and/or MCI patients from controls [28][29][30][31][32][33][34][35][36][37][38][39], as well as a number of review articles [22,[40][41][42][43]. Two studies of most note include contributions by O'Bryant and colleagues [44] and Doecke and colleagues [45] who identified algorithmic signatures of multivariate analytes in large, well-characterised cohorts with AUC characteristics of at least 93% in serum and plasma, respectively.…”

The Plasma Amyloid Beta 42 (Aβ42) and Proteomics Profile Related to Canine Cognitive Dysfunction Syndrome (CCDS) in Thailand

“…The clearance of Aβ occurs by binding with soluble Aβ to prevent aggregation and increase degrading mechanisms [21]. Many studies have suggested that alpha-2-macroglobulin, apolipoproteins, transthyretin, clusterin and the complement system are involved in AD pathogenesis through the sequestration of Aβ, leading to increased Aβ clearance in vivo [64][65][66][67]. Transthyretin and clusterin are sequester proteins that function as inhibitors of Aβ bril formation and further suppress the toxicity of oligomers.…”