DT‐01‐05: TEMPORAL LOBE QUANTITATION OF FLORTAUCIPIR PET IMAGES MAY IMPROVE DETECTION OF INTERMEDIATE NEUROFIBRILLARY TANGLE PATHOLOGY IN AUTOPSY‐VALIDATED CASES

Abstract

Background: In the present study, we examined the performance of the novel tau PET ligand [ 18 F]RO948 in discriminating AD from non-AD disorders. This included a comparison with established MRI and CSF measures, as well as a head-to-head component between [ 18 F]RO948 and [ 18 F]flortaucipir uptake in a subset of patients with semantic variant primary progressive aphasia (svPPA). Methods: [ 18 F]RO948 PET data was acquired for 543 subjects from the Swedish BioFINDER-2 study. Diagnostic groups included cognitively unimpaired (CU; n231), mild cognitive impairment (n135), AD dementia (n86), and varied non-AD disorders (n91) (i.e. bvFTD, svPPA, DLB, PD/PDD, PSP, MSA and VaD). FreeSurfer-based ROIs were combined into predefined composite Braak regions (I-IV, I-II, III-IVand V-VI) and used to sample parametric SUVR images (reference region, inferior cerebellum). Area under the receiver operating characteristic curve (AUC) analyses was performed in comparison to hippocampal volume, composite temporal and whole-brain cortical thickness, and CSF measures (Ab42/P-tau combined with NFL). In the three svPPA cases that underwent both [ 18 F]flortaucipir and [ 18 F]RO948 PET, subtraction images were created in order to examine differences in tracer retention. Results: [ 18 F]RO948 SUVR levels within Braak regions were higher in AD compared to all other diagnostic groups (Figure [ 18 F]RO948 showed high accuracy for distinguishing AD dementia from CU subjects (Figure [ 18 F]RO948 AUC values were higher than those for MRI and CSF measures, and were greatest when using the Braak I-IV region (AUC 0.983 compared to CU subjects, and 0.969 when compared to all non-AD disorders) (Figure Generally, [ 18 F]RO948 Braak I-IV positivity was only seen in amyloid-positive cases or in MAPT R406W mutation carriers. [ 18 F] RO948 was below the cut off also in svPPA, and head-to-head comparison of [ 18 F]flortaucipir and [ 18 F]RO948 in three cases with svPPA showed that temporal lobe uptake was lower with [ 18 F] RO948.