Antagonistic Amyloid‐β and tau interactions with T1‐weighted/T2‐weighted magnetic resonance ratio in Alzheimer’s disesase continuum

Abstract

AbstractBackgroundTau protein has been reported as a major cause of neurodegeneration in Alzheimer’s disease (AD) continuum. Decrease of T1‐weighted/T2‐weighted magnetic resonace (MR) ratio has been proposed as a measure of demyelination related to neurodegeneration, but some previous researches showed contradictory increase in several brain regions, which was considered as the effecs of other microstructures such as the amyloid‐related iron deposition. Therefore, amyloid β and tau proteins appear to affect the T1w/T2w ratio antagonistically, making their relationship need to be elucidated in order to unambiguously interpret the ratio.MethodWe obtained 221 individuals which include T1‐ and T2‐weighted MR images, and 18F‐florbetapir‐ and 18F‐flortaucipir‐PET images from ADNI. The subjects were then divided into four subgroups based on the status of global Aβ and tau accumulation amount: A‐T‐, A‐T+, A+T‐, and A+T+. We determined positive amyloid status(A+) as global Aβ PET SUVR > 1.11. When determining tau positivity, we used entorhinal cortex (EC) as the earliest tau accumulation region to selectively include tau‐negative individuals while amyloid is being presented. Group differences in regional T1w/T2w ratio values were evaluated.ResultWe found significant group differences in various cortical regions, but also observed distinct effects of Aβ and tau for the T1w/T2w difference. First of all, Aβ and tau affect the T1w/T2w ratio in an opposite direction. A+ individuals have greater T1w/T2w ratio values across wide cortical regions compared to A‐ individuals for both T‐ and T+ groups. However, A‐T+ groups have smaller T1w/T2w ratio values than A‐T‐ groups, while the significant group difference was observed across relatively few cortical regions. Second, Aβ has stronger effect on the T1w/T2w ratio than tau. Specifically, the group difference between A+T+ and A+T‐ shows that Aβ increase the ratio values more strongly than tau reduces the ratio values due to greater accumulation of Aβ in the A+T+ than A+T‐.ConclusionIn this work, we observed the antagonistic interaction of Aβ and tau with T1w/T2w ratio, while more interestingly, we also found that Aβ causes high T1w/T2w ratio, more than tau causes demyelination, followed by lowering T1w/T2w ratio.