Flortaucipir PET uncovers relationships between tau and β-amyloid in aging, primary age related tauopathy, and Alzheimer disease

[18F]-Flortaucipir PET is considered a good biomarker of Alzheimer’s disease. However, it is unknown how flortaucipir is associated with the distribution of tau across brain regions and how these associations are influenced by β-amyloid. It is also unclear whether flortaucipir can detect tau in definite primary age-related tauopathy (PART). We identified 248 individuals at Mayo Clinic that had undergone [18F]-flortaucipir PET during life, had died, and undergone an autopsy, 239 cases of which also had β-amyloid PET. We assessed nonlinear relationships between flortaucipir uptake in nine medial temporal and cortical regions, Braak tau stage and Thal β-amyloid phase using generalized additive models. We found that flortaucipir uptake was greater with increasing tau stage in all regions. Increased uptake at low tau stages in medial temporal regions was only observed in cases with high β-amyloid phase. Flortaucipir uptake linearly increased with β-amyloid phase in medial temporal and cortical regions. The highest flortaucipir uptake occurred with high Alzheimer’s disease neuropathologic change (ADNC) scores, followed by low-intermediate ADNC scores, then PART, with entorhinal cortex providing the best differentiation between groups. Flortaucipir PET had limited ability to detect PART and imaging defined PART did not correspond with pathologically defined PART. In summary, spatial patterns of flortaucipir mirrored histopathological tau distribution, were influenced by β-amyloid phase, and were useful for distinguishing different ADNC scores and PART.

Methods
These data are from 248 participants recruited from Mayo Clinic, Rochester, MN, who had flortaucipir PET imaging during life, had died, and had undergone an autopsy evaluation. All patients were enrolled into one of three NIH funded cohort studies including the Mayo Clinic Alzheimer’s Disease Research Center (PI: Petersen), The Mayo Clinic Study of Aging (PI: Petersen) and the Neurodegenerative Research Group (PIs: Josephs/Whitwell).