Abstract
IntroductionOligomeric 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.MethodsWe 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.ResultsWe 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.DiscussionFindings 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.
Highlights
Oligomeric amyloid-ß is a major toxic species associated with Alzheimer’s disease pathogenesis
It showed tendency to increase from healthy normal controls (HNC) to subjective cognitive decline (SCD), mild cognitive impairment (MCI) and Alzheimer’s disease (AD) (ANOVA, p < 0.001), and there was a significant difference from MCI and AD compared to HNC level, but there were age differences between them (Tukey multiple comparison of means, p < 0.01) (Table 1)
voxel-based morphology (VBM) analyses of the grey matter (GM) and white matter (WM) Table 2 and Fig. 2 show significant GM and WM volume change in relation to the oligomerization level measured by MDS-OAß and VBM analysis in all spectrum of subjects which includes HNC, SCD, MCI and AD dementia
Summary
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. Aβ is produced by cleavage of amyloid precursor proteins into a monomeric form by β-secretase and γ-secretase, which is transformed into oligomeric form and fibre form, and into amyloid plaques [4]. Oligomeric Aβ is the major toxic species of Aβ associated with AD pathology as well as synaptic dysfunction [5, 6], and this could be the final target of AD biomarker. New methods, advanced in terms of invasiveness and cost and aimed at measuring oligomeric Aß in the blood, emerged in numbers
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