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

Abstract

BackgroundSoluble amyloid-β (Aβ) oligomers are the major toxic substances associated with the pathology of Alzheimer’s disease (AD). The ability to measure Aβ 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 Aβ oligomers selectively, was used to detect Aβ oligomers in the plasma of patients with AD and healthy control individuals.MethodsTwenty-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 Aβ42, phosphorylated tau protein (pTau), and total tau protein (tTau); and 11C-Pittsburgh compound B (PIB) positron emission tomography. Pearson’s correlation analyses between the estimations of Aβ oligomer levels by MDS and other conventional AD biomarkers (CSF Aβ42, 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.ResultsThe plasma levels of Aβ oligomers by MDS were higher in patients with AD than in normal control individuals, and they correlated well with conventional AD biomarkers (levels of Aβ oligomers by MDS vs. CSF Aβ42, 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 Aβ oligomers by MDS for differentiating AD from the normal controls were 78.3% and 86.5%, respectively. The AUC for plasma Aβ oligomers by MDS was 0.844, which was not significantly different from the AUC of other biomarkers (p = 0.250).ConclusionsPlasma levels of Aβ oligomers could be assessed using MDS, which might be a simple, noninvasive, and accessible assay for evaluating brain amyloid deposition related to AD pathology.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-017-0324-0) contains supplementary material, which is available to authorized users.

Association of Plasma Oligomerized Beta Amyloid with Neurocognitive Battery Using Korean Version of Consortium to Establish a Registry for Alzheimer’s Disease in Health Screening Population

“…A previous study confirmed that the plasma OAβ level increases in plasma of AD patients but does not increase in the plasma of healthy normal control [12]. The increase in the plasma AβO level in AD highly correlates with CSF Aβ42 and Pittsburgh compound B (PiB) PET standard uptake ratio [13]. In addition, the elevated plasma OAβ level showed a strong correlation with cognitive performance in patients with AD, including an inverse correlation with scores on the mini-mental status examination (MMSE), cognitive abilities screening instrument, the common objects memory test, and a positive correlation with the Alzheimer's disease assessment scale-cognitive portion scores [14].…”

Current state of Alzheimer’s fluid biomarkers

“…Different technologies have been investigated and some have shown promise; examples include ELISA-based methods in CSF [143, 312, 396] and in plasma [381], single-molecule fluorescence microscopy in CSF [144], and a protein misfolding cyclic amplification assay method in CSF [308]. However, the overall findings have been inconsistent or unsatisfactory (reviewed by Schuster and Funke [318]).…”

Plasma amyloid beta levels are associated with cerebral amyloid and tau deposition

“…A number of studies have suggested that plasma Ab42 and Ab40 measures, as well as the ratio of Ab42/ Ab40 are reduced in patients with AD and MCI and that these plasma biomarkers can predict the presence of AD and MCI and progression from normal to impaired cognition [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. However, other studies have shown that higher plasma Ab measures are associated with AD and conversion to AD [19][20][21][22][23][24]. Still, others have found no significant relationship [25,26].…”

“…Reduced plasma Ab has also been linked to poorer cognition [6,7,19,21,[27][28][29][30]. In addition, some studies have suggested that plasma levels of Ab42 and Ab40 are associated with the levels of cerebral Ab on positron emission tomography (PET), cerebrospinal fluid levels of Ab and tau, and AD-like brain atrophy [4,7,8,11,16,17,24,[31][32][33][34][35][36][37][38], while others have not seen such an association [25,39,40]. These conflicting results may be due to the type of plasma markers measured and the methodologies used to extract these values.…”