Free diffusion increases coinciding with enhanced glymphatic clearance during initial tau burden loading in a mouse model of tauopathy determined using NODDI and contrast enhanced MRI

摘要

In the rTg4510 Alzheimer disease model pathology starts in the cortex and spreads over time in a prion like manner to connected regions of the hippocampus and frontal/temporal cortices, and finally to the striatum and thalamus but the cerebellum is spared. The tangles are observed in the cortex by 4 months of age, the hippocampus by 5.5 months (1) with cortical cell loss occurring at 8.5 months (2). In this process glial cells lose some homeostatic function acquiring a proinflammatory phenotype believed to precede neurodegeneration (3). In this study we demonstrate increased CSF ICF exchange in the presence of the proposed neuroinflammation marker of free/isotropic diffusion (4) at the initial onset of tau loading in the striatum and thalamus at 8.5 months.