Plasma oligomer βeta‐amyloid and white matter microstructural integrity in cognitively normal older adults according to cerebral amyloid deposition

Abstract

AbstractBackgroundMultimer detection system‐oligomeric amyloid‐ß (MDS‐OAß) measures plasma OAß level, which is associated with earlier pathology of Alzheimer’s disease (AD). Previous studies showed that plasma levels of MDS‐OAβ were higher in patients with dementia due to AD than in cognitive normal older adults (CN), and they correlated well with conventional AD biomarkers including standardized uptake value ratio (SUVR) of Pittsburgh compound B (PiB) and CSF level of Aβ42, p‐Tau, and t‐Tau. However, no previous study investigated MDS‐OAβ difference in CN with or without cerebral Aβ burden. In addition, associations among MDS‐OAß, cerebral Aß deposition, aberrance of white matter integrity, and cortical thickness in CN is not elucidated.MethodWe studied 34 CN with amyloid‐PET negative and 23 CN with amyloid‐PET positive results who received MDS‐OAβ, structural MRI, and diffusion tensor imaging (DTI).ResultAmyloid‐PET positive group showed higher MDS‐OAß level than amyloid‐PET negative group, but two groups did not differ in WM integrity or cortical thickness. MDS‐OAβ level was significantly higher in amyloid‐PET positive group than in amyloid‐PET negative group. MDS‐OAβ positive group had significantly higher cerebral AB deposition, or mean global SUVR values, than MDS‐OAβ negative group. There was a positive correlation between MDS‐OAβ level and PET‐SUVR. In terms of DTI analysis, MDS‐OAβ positive group had significantly lower FA in the left forceps minor of corpus callosum and right superior longitudinal fasciculus than in lower MDS‐OAβ negative group. In addition, the FA values were negatively correlated with MDS‐OAβ level (figure 1). MDS‐OAB positive group showed a significant reduction in the cortical thickness in the left fusiform when compared with the MDS‐OAB negative groupConclusionPlasma MDS‐OAβ value might reflect cerebral amyloid status and global cerebral Aß retention in CN. We elucidated toxic role of OAβ by showing that the plasma OAβ value were associated with decrement of WM microstructural integrity in the early pathological process of AD. Cortical thickness did not differ according to cerebral Aβ burden but rather was associated with higher plasma OAβ level. Thus, MDS‐OAβ value might reflect earlier, and different, pathology than cerebral Aß retention measured using amyloid PET scan in CN with AD continuum.