Structural MRI signature predicts tau staging in Alzheimer's disease
Abstract INTRODUCTION Tau positron emission tomography (PET) probes Alzheimer's disease (AD) severity via regional tau spread but is not widely available. We tested whether multiregion structural magnetic resonance imaging (MRI) could approximate individual tau burden. METHODS We studied 378 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with mild cognitive impairment (MCI)‐AD or AD dementia with paired T1‐MRI and [18F]flortaucipir tau‐PET (≤6 months apart). Regional cortical thickness and volume were extracted with FreeSurfer. Principal component analysis and multivariable linear regression yielded MRI signatures of tau‐PET standardized uptake value ratio (SUVR) in Braak composite regions (I, III–IV, V–VI), a meta‐temporal region of interest (ROI), and a global neocortical meta‐ROI. Performance and high/low tau classification were evaluated by leave‐one‐out cross‐validation against published cut‐offs. RESULTS MRI signatures were significantly associated with tau‐PET burden across all regions (p < 0.001). High‐versus‐low tau discrimination varied: AUC ≈ 0.70 in Braak I, ≈0.89 in Braak V–VI, and ≈0.90 globally. Discussion Here we provide proof‐of‐concept evidence that multiregion T1‐MRI patterns can inform on tau‐PET burden in AD and may support approximate tau staging when tau‐PET is unavailable, especially in subjects with more advanced tau burden.