Amyloid-dependent and amyloid-independent effects of Tau in individuals without dementia

• Autor(a) principal: Therriault, Joseph
• Data de Publicação: 2021
• Outros Autores: Pascoal, Tharick Ali, Sefranek, Marcus, Mathotaarachchi, Sulantha Sanjeewa, Benedet, Andréa L., Chamoun, Mira, Lussier, Firoza Z., Tissot, Cecile, Bellaver, Bruna, Ferreira, Pâmela Lukasewicz, Zimmer, Eduardo Rigon, Saha-Chaudhuri, Paramita, Gauthier, Serge G., Rosa Neto, Pedro
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/232648
• topic: Peptídeos beta-amilóides; Proteínas tau; Disfunção cognitiva; Tauopatias

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 [18F]AZD4694, tau-PET with [18F]MK6240, structural MRI, and neuropsychological testing. We also evaluated an independent cohort of 240 individuals who were assessed with amyloid-β PET with [18F]Florbetapir, tau-PET with [18F]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 < 0.001). We also observed in both cohorts that in regions of the neocortex, associations between neocortical tau-PET and clinical function were dependent on local amyloid-PET (FWE corrected at p < 0.001). Interpretation: In medial temporal brain regions, characterized by the accumulation of tau pathology in the absence of amyloid-β, tau had direct associations with cognitive dysfunction. In brain regions characterized by the accumulation of both amyloid-β and tau pathologies such as the posterior cingulate and medial frontal cortices, tau’s relationship with cognitive dysfunction was dependent on local amyloid-β concentrations. Our results provide evidence that amyloid-β in Alzheimer’s disease influences cognition by potentiating the deleterious effects of tau pathology.