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.