IC-P-040: EVALUATION OF TAU DEPOSITION IN AMYLOID POSITIVE MCI OR MILD-AD DEMENTIA SUBJECTS FROM THE ELENBECESTAT MISSION AD PROGRAM USING [¹⁸ F]PI-2620 PET

[18F]PI-2620 is a novel tau PET-tracer that accumulates in regions of tau pathology. The study objective was to evaluate regional tau deposition using [18F]PI-2620 PET tracer in a sub-study of the elenbecestat MissionAD program in patients with MCI due to AD or mild AD dementia. Patient sub-study inclusion criteria were: MCI due to AD or mild AD dementia including: MMSE ≥ 24, CDR global score of 0.5, CDR Memory Box score ≥ 0.5, and impaired episodic memory confirmed by a list learning task. All subjects were amyloid PET positive by visual read. 45 subjects underwent [18F]PI-2620 PET scans from 60–90 min p.i. (mean age 76 ± 7 yrs). Composite regions-of-interest (ROIs) were used to index uptake within mesial-temporal, temporoparietal and the rest of the neocortex (MeTeR regions, Villemagne, 2017). Cerebellar cortex was used as reference region (vermis and anterior cerebellar gray matter contiguous to the vermis was excluded). Individual MRI-based subregions including hippocampus (HC) and parahippocampus (PHC) were further investigated. Of the 45 subjects evaluated, 27 subjects were tau PET positive upon visual inspection. 13 subjects had obvious [18F]-PI-2620 neocortical PI-2620 accumulations extending outside of the mesial-temporal cortex. An additional 14 subjects had subtle accumulations. In examining these subjects, 12 had uptake restricted within HC/PHC ROIs, one had diffuse cortical uptake and one had a lateralized focal accumulation in parietal cortex. The HC/PHC ROIs were characterized by uptake >2SD in the Me-region compared to a database of non-demented controls (n=10) or visual inspection of the specific PHC/PC regions. 18 subjects were considered tau PET negative. The age of the subjects in these three categories did not differ significantly (p>0.5). The MissionAD tau PET imaging sub-study is still recruiting subjects for baseline tau PET scans. [18F]PI-2620 accumulation was observed in 60% of the studied subjects with MCI due to AD/mild AD. 44% of the apparent tau positive cases had isolated mesial temporal uptake consistent with early disease. These subjects are expected to be an ideal cohort for therapeutic interventions. The addition of [18F]PI-2620 imaging into clinical trials is feasible and provides valuable information about the subject profile.