Data from: Intermediate Flortaucipir uptake is associated with A&[beta]-PET & CSF-tau in asymptomatic adults

Objective: To investigate relationships between tau-PET binding and other established Alzheimer's disease (AD) markers in cognitively normal individuals at increased risk of AD. Methods: One-hundred-nineteen late-middle-aged and older adults with a parental or multiple-sibling history of AD (PREVENT-AD cohort, mean age=67±5) underwent tau PET ([18F]flortaucipir), β-amyloid (Aβ) PET ([18F]NAV4694), and cognitive assessment. A subsample of 74 participants also had CSF phosphorylated (p)-tau data available. We investigated regional tau SUVR differences between Aβ-positive and Aβ-negative individuals using general linear models adjusted for age and sex. In regions showing higher flortaucipir binding in Aβ-positive individuals, we assessed whether flortaucipir SUVRs were related to p-tau and cognitive performance. We repeated these analyses iteratively removing the participant with the highest entorhinal flortaucipir SUVR to determine thresholds at which associations with Aβ-PET, CSF p-tau and cognition were detectable. Results: Aβ-positive individuals had higher flortaucipir SUVRs than Aβ-negative ones in limbic, temporal, occipital, and inferior parietal regions. Increased flortaucipir SUVRs in a subset of predominantly medial temporal regions were also associated with increased CSF p-tau and worse cognitive performance. The association of flortaucipir in the entorhinal cortex with CSF p-tau, Aβ, or delayed memory were inapparent among individuals with SUVRs below 1.12, 1.23 and 1.41 respectively. Conclusions: Flortaucipir binding in AD-typical regions is associated with established AD markers. Except for the association of flortaucipir-binding with cognition, these findings were not driven by results in individuals classified as tau-positive according to conventional tau thresholds. These observations suggest that early (sub-threshold) elevation in flortaucipir signal is clinically meaningful.Intermediate Flortaucipir Paper: Supplementary MaterialSupplementary methods for the amyloid-beta Gaussian mixture model, supplementary cognitive index results, and results of the analyses run with partial-volume corrected data.aug13_neurology_supplementary methods.doc