Frigerio, Irene;
Boon, Baayla DC;
Lin, Chen-Pei;
Graaf, Yvon Galis-de;
Bol, John GJM;
Preziosa, Paolo;
Twisk, Jos;
... Jonkman, Laura; + view all
(2021)
Amyloid-β, p-tau, and reactive microglia load are correlates of MRI cortical atrophy in Alzheimer's disease.
BioRxiv: Cold Spring Harbor, NY, USA.
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Abstract
INTRODUCTION: The aim of this study was to identify the histopathological correlates of MRI cortical atrophy in (a)typical Alzheimer’s disease (AD) donors. METHODS: 19 AD and 10 control donors underwent post-mortem in-situ 3T-3DT1-MRI, from which cortical thickness was calculated. Upon subsequent autopsy, 21 cortical brain regions were selected and immunostained for amyloid-beta, phosphorylated-tau, and reactive microglia. MRI-pathology associations were assessed using linear mixed models. Post-mortem MRI was compared to ante-mortem MRI when available. RESULTS: Higher amyloid-beta load weakly correlated with a higher cortical thickness globally. Phosphorylated-tau strongly correlated with cortical atrophy in temporo-frontal regions. Reactive microglia load strongly correlated with cortical atrophy in the parietal region. Post-mortem scans showed high concordance with ante-mortem scans acquired <1 year before death. DISCUSSION: Distinct histopathological markers differently correlate with cortical atrophy, highlighting their different roles in the neurodegenerative process. This study contributes in understanding the pathological underpinnings of MRI atrophy patterns.
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