Oligomeric forms of amyloid-beta protein in plasma as a potential blood-based biomarker for Alzheimer's disease

Abstract

Background: Soluble amyloid-beta (A beta) oligomers are the major toxic substances associated with the pathology of Alzheimer's disease (AD). The ability to measure A beta oligomer levels in the blood would provide simple and minimally invasive tools for AD diagnostics. In the present study, the recently developed Multimer Detection System (MDS) for AD, a new enzyme-linked immunosorbent assay for measuring A beta oligomers selectively, was used to detect A beta oligomers in the plasma of patients with AD and healthy control individuals. Methods: Twenty-four patients with AD and 37 cognitively normal control individuals underwent extensive clinical evaluations as follows: blood sampling; detailed neuropsychological tests; brain magnetic resonance imaging; cerebrospinal fluid (CSF) measurement of A beta 42, phosphorylated tau protein (pTau), and total tau protein (tTau); and C-11-Pittsburgh compound B (PIB) positron emission tomography. Pearson's correlation analyses between the estimations of A beta oligomer levels by MDS and other conventional AD biomarkers (CSF A beta 42, pTau, and tTau, as well as PIB standardized uptake value ratio [ PIB SUVR]) were conducted. ROC analyses were used to compare the diagnostic performance of each biomarker. Results: The plasma levels of A beta oligomers by MDS were higher in patients with AD than in normal control individuals, and they correlated well with conventional AD biomarkers (levels of A beta oligomers by MDS vs. CSF A Chi 42, r = -0.443; PIB SUVR, r = 0.430; CSF pTau, r = 0.530; CSF tTau, r = 0.604). The sensitivity and specificity of detecting plasma A beta oligomers by MDS for differentiating AD from the normal controls were 78.3% and 86.5%, respectively. The AUC for plasma A beta oligomers by MDS was 0.844, which was not significantly different from the AUC of other biomarkers (p = 0.250). Conclusions: Plasma levels of A beta oligomers could be assessed using MDS, which might be a simple, noninvasive, and accessible assay for evaluating brain amyloid deposition related to AD pathology.