Blood amyloid-β oligomerization associated with neurodegeneration of Alzheimer’s disease

Abstract

Introduction Oligomeric amyloid-ß is a major toxic species associated with Alzheimer’s disease pathogenesis. Methods used to measure oligomeric amyloid-β in the blood have increased in number in recent years. The Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) is a specific method to measure oligomerization tendencies in the blood. The objective of this study was to determine the association between amyloid-ß oligomerization in the plasma and structural changes of the brain. Methods We studied 162 subjects composed of 92 community-based normal healthy subjects, 17 with subjective cognitive decline, 14 with mild cognitive impairment and 39 with Alzheimer’s disease dementia. All subjects underwent MDS-OAβ and three-dimensional T1 magnetic resonance imaging. To determine the structural changes of the brain that are statistically correlated with MDS-OAβ level, we used voxel-based morphometry with corrections for age and total intracranial volume covariates. Results We found brain volume reduction in the bilateral temporal, amygdala, parahippocampal and lower parietal lobe and left cingulate and precuneus regions (family-wise error, p < 0.05). Reduction was also found in white matter in proximity to the left temporal and bilateral lower parietal lobes and posterior corpus callosum (family-wise error, p < 0.05). Brain volume increment was not observed in any regions within grey or white matter. Discussion Findings suggest that substantial correlation exists between amyloid ß oligomerization in the blood and brain volume reduction in the form of Alzheimer’s disease despite of uncertainty in the casual relationship. Electronic supplementary material The online version of this article (10.1186/s13195-019-0499-7) contains supplementary material, which is available to authorized users.

Dynamic Blood Concentrations of Aβ1–40 and Aβ1–42 in Alzheimer’s Disease

“…First, the Aβ 1−42 aggregation process is continuous, from monomer, oligomer, protofibril, and eventually to fibril forms (Sinha and Lieberburg, 1999;Selkoe and Hardy, 2016). Compared to healthy subjects, the plasma of AD patients has been hypothesized to have a tendency to foster Aβ 1−42 aggregation (Haass and Selkoe, 2007;Youn et al, 2019). Consistent with this hypothesis, the detected Aβ 1−42 plasma levels increased from baseline to 24 h in this study.…”

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

“…Furthermore, the decrease in the CERAD score in the order of normal individuals, MCI, and AD correlated with the atrophy of white matter lesions and gray matter in the brain [27], and scores for the word list recall and memory from the CERAD had a close relationship with atrophy in the medial temporal lobe [28]. In addition, the study by Youn et al [16] confirmed that the correlation between the change in the MDS-OAβ value and brain atrophy in the form of AD exists. The cross-sectional and longitudinal evidence of connections among neurodegeneration, blood OAβ, and cognitive impairment in predementia status should be sought in future studies.…”

“…Prior to the assay, aliquots of plasma samples were thawed at 37 • C for 15 min. All protocols were the same as in our previous papers [12,15,16]. As indicated in the assay protocol of the inBlood TM OAß Test, PBR-1 (purified synthetic Aβ made by PeopleBio Inc.) was spiked into plasma and the mixture was incubated at 37 • C for 48 h. The incubated plasma sample mixture and serially diluted standard samples were added to each well of the plates.…”

Hebbian and Homeostatic Synaptic Plasticity—Do Alterations of One Reflect Enhancement of the Other?

“…The role of APP processing via the amyloidogenic pathway has been studied in detail for its pathogenic role in neurodegeneration (Goldsworthy and Vallence, 2013;Nieweg et al, 2015;Gupta and Goyal, 2016;Chen et al, 2017;Youn et al, 2019). What remains less understood is the physiological role of the amyloidogenic processing pathway and Aβ.…”