Tau positron emission tomography analysis methods for the quantification of tau spread in preclinical and early Alzheimer's disease

INTRODUCTION: Inhibition of pathological tau spread may slow cognitive decline in Alzheimer's disease. Here, we evaluate two tau positron emission tomography (PET) analysis methods designed for detecting tau spread. METHODS: Spatial progression of tauopathy (SPOT) and tau-naïve anatomical region of interest (tau-naïve ROI) methods were assessed in two large observational cohorts in amyloid-positive (A+) cognitively unimpaired (CU) or mildly cognitively impaired (MCI) participants versus CU amyloid-negative (A-) participants. RESULTS: SPOT and tau-naïve ROI demonstrated measurable annualized change in CU A+ and MCI A+ participants versus CU A- participants. These spread estimates produced effect sizes comparable to standardized uptake value ratio (SUVR) change measures in anatomically defined ROIs. Effect sizes were increased when evaluating the subset of tau positive CU A+ and MCI A+ participants. DISCUSSION: SPOT and tau-naïve ROI methods are designed to measure tau spread and may be used in addition to traditional SUVR measures to evaluate tau progression in AD.