IC‐P‐175: IN VIVO COMPARISON OF TAU PET RADIOLIGANDS 18F‐THK‐5351 AND 18F‐MK‐6240

Background: The extent to which older adults follow a typical pattern of tau-PET deposition is not clear. We focused on interindividual pattern of flortaucipir ([F]AV1451) binding across Braak stages and single brain regions in participants along the AD spectrum. Methods: We included 166 Ab-negative (113 cognitively normal [CN], 33 eMCI, and 20 lMCI/AD) and 129 Ab-positive (72 CN, 30 eMCI and 27 lMCI/AD) participants from ADNI with a flortaucipir PET scan. SUVRs were extracted in composite regions approximating Braak stages and in the Freesurfer Desikan atlas regions as more fine-grained measurements. In each region, we derived liberal and conservative thresholds using Gaussianmixture models (GMM) across all participants (respectively 50% and 90% probability to be in high SUVR distribution). We then examined the distribution of elevated SUVR across all regions at the subject-level. Results: Even when applying liberal thresholds for positivity, only 4% of Ab-negative participants had elevated SUVR in Braak I/entorhinal and/or in further stages (Fig.1A). In Ab-positive subjects, 17% CN, 43% EMCI and 67% LMCI/AD had elevated SUVR in Braak I (Fig.1B and Fig.2). Among these individuals, only 50% of LMCI/AD had elevated SUVRs in further stages compared to 92% in EMCI. Using smaller regions, flortaucipir spreading became evident in LMCI/AD and 8% of CN showed focal cortical binding in the absence of elevated entorhinal SUVR (Fig.2). Conclusions: Almost no Ab-negative individuals have elevated tau, regardless of clinical diagnosis. All Ab-positive participants followed the expected pattern of tau spreading, when using composite Braak regions, but only 50% of LMCI/AD showed abnormal binding outside of the entorhinal cortex even with liberal thresholds. Using smaller regions revealed widespread tau in LMCI/AD. Furthermore, some CN individuals did not follow the expected spatiotemporal progression of tau. This unexpected focal binding in CNmight indicate non-AD neurodegenerative disease or false positive results.