Introduction: In Alzheimer's disease (AD), hyperphosphorylated tau is closely associated with focal neurodegeneration, but the mechanism remains uncertain.
Methods: We quantified cortical microstructure using neurite orientation dispersion and density imaging in 14 individuals with young onset AD. Diffusion tensor imaging measured mean diffusivity (MD). Amyloid beta and tau positron emission tomography were acquired and associations with microstructural measures were assessed.
Results: When regional volume was adjusted for, in the medial temporal lobe there was a significant negative association between neurite density and tau (partial R2 = 0.56, p = 0.008) and between orientation dispersion and tau (partial R2 = 0.66, p = 0.002), but not between MD and tau. In a wider cortical composite, there was an association between orientation dispersion and tau (partial R2 = 0.43, p = 0.030), but not between other measures and tau.
Discussion: Our findings are consistent with tau causing first dendritic pruning (reducing dispersion/complexity) followed by neuronal loss. Advanced magnetic resonance imaging (MRI) microstructural measures have the potential to provide information relating to underlying tau deposition.
Keywords: Alzheimer's disease; cerebral cortex; diffusion MRI; microstructure; neurite orientation dispersion and density imaging; positron emission tomography; tau.
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.