White matter (WM) microstructure abnormalities have been observed in prodromal and manifest Alzheimer’s disease (AD). However, the precise nature and sequence of WM neurodegeneration across the disease course is unclear. Here, we leverage state-of-the-art disease progression modelling to sequence WM microstructure abnormalities in AD, as quantified by diffusion MRI in the ADNI study. We observe WM abnormalities among the earliest AD structural abnormalities and characterise the precise sequence of WM neurodegeneration. This fine-grained approach may be used to identify subjects at early disease stages for participation in therapeutic clinical trials.
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