Amyloid-dependent and amyloid-independent effects of Tau in individuals without dementia.
Therriault J., Pascoal TA., Sefranek M., Mathotaarachchi S., Benedet AL., Chamoun M., Lussier FZ., Tissot C., Bellaver B., Lukasewicz PS., Zimmer ER., Saha-Chaudhuri P., Gauthier S., Rosa-Neto P., Alzheimer's Disease Neuroimaging Initiative None.
OBJECTIVE: To investigate the relationship between the topography of amyloid-β plaques, tau neurofibrillary tangles, and the overlap between the two, with cognitive dysfunction in individuals without dementia. METHODS: We evaluated 154 individuals who were assessed with amyloid-β PET with [18 F]AZD4694, tau-PET with [18 F]MK6240, structural MRI, and neuropsychological testing. We also evaluated an independent cohort of 240 individuals who were assessed with amyloid-β PET with [18 F]Florbetapir, tau-PET with [18 F]Flortaucipir, structural MRI, and neuropsychological testing. Using the VoxelStats toolbox, we conducted voxel-wise linear regressions between amyloid-PET, tau-PET, and their interaction with cognitive function, correcting for age, sex, and years of education. RESULTS: In both cohorts, we observed that tau-PET standardized uptake value ratio in medial temporal lobes was associated with clinical dementia rating Sum of Boxes (CDR-SoB) scores independently of local amyloid-PET uptake (FWE corrected at p