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AbstractIntroductionTau‐positron emission tomography (PET) imaging with AV1451 is sensitive to Alzheimer disease (AD)–related tau deposition in the brain. We (1) examined regional variation of average tau‐PET standardized uptake value ratios (SUVRs) in a young normal population (30–49 years) and corrected for the regional variability and (2) tested if the standardized values (z‐scores) scaled appropriately to capture regional Alzheimer‐specific (i.e., amyloid sensitive) tau‐PET changes in individuals aged 50+ years.MethodsWe identified 490 individuals (70 between 30–49 years as a reference group and 420 cognitively normal between 50–95 years of age) with tau‐PET and amyloid PET scans from the Mayo Clinic Study of Aging.ResultsThere was intrinsic regional variability in average tau‐PET SUVR with uptakes higher in some regions than others, even in the younger individuals who would have minimal or no neurofibrillary tangles. We corrected for this using region of interest–specific z‐scores based on the reference group. Amyloid and tau‐PET uptake were associated throughout the brain after adjusting for age, with the highest correlations in the medial temporal regions.DiscussionRegions with high‐average SUVR are not necessarily those with the greatest tau pathology. Standardization is therefore recommended. Standardization of the data “realigns” the data such that the regional tau z‐scores are informative of the disease process, that is, regions with high z‐scores now coincide with regions correlated with amyloid deposition. Medial temporal structures, specifically entorhinal cortex–tau, may be useful as an AD‐specific tau‐PET signature due to its sensitivity to amyloid.