RESEARCH Open Access Blood amyloid-β oligomerization associated with neurodegeneration of Alzheimer’ s disease Young Chul Youn 1 , Sungmin Kang 2 , Jeewon Suh 3 , Young Ho Park 3 , Min Ju Kang 3,4 , Jung-Min Pyun 4 , Seong Hye Choi 5 , Jee Hyang Jeong 6 , Kyung Won Park 7 , Ho-Won Lee 8 , Seong Soo A. An 9 , Jacqueline C. Dominguez 10 and SangYun Kim 3* 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. Keywords: Oligomerization, Blood-based biomarker, Amyloid β, Oligomer, Multimer detection system, Voxel- based morphometry, Multimer detection system-oligomeric Aβ Introduction Biomarkers play an important role in the diagnosis, sta- ging and the risk assessment of disease. Especially, in clin- ical trials of disease-modifying drugs for Alzheimer’ s disease (AD), the biomarker is necessary in selecting sub- jects and predicting responders to a specific drug inter- vention and monitoring the responsiveness. Extracellular accumulation of amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles is the characteristic feature of AD [1–3]. 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 finally into amyloid plaques [4]. Among them, oligomeric Aβ is the major toxic species of Aβ associated with AD pathology as well as synaptic dys- function [5, 6], and this could be the final target of AD biomarker. Currently validated amyloid biomarkers of AD are cerebrospinal fluid Aβ1–42 level and amyloid positron emission tomography imaging [7]. However, there are some limitations, such as invasiveness, interlaboratory variability, and cost. Many researchers have focused on the identification of blood-based biomarkers for AD but, © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. * Correspondence: neuroksy@snu.ac.kr 3 Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea Full list of author information is available at the end of the article Youn et al. Alzheimer's Research & Therapy (2019) 11:40 https://doi.org/10.1186/s13195-019-0499-7