Distinct effects of beta-amyloid and tau on cortical thickness in cognitively healthy older adults

Introduction Published reports of associations between beta-amyloid (A beta) and cortical integrity conflict. Tau biomarkers may help elucidate the complex relationship between pathology and neurodegeneration in aging. Methods We measured cortical thickness using magnetic resonance imaging, A beta using Pittsburgh compound B positron emission tomography (PiB-PET), and tau using flortaucipir (FTP)-PET in 125 cognitively normal older adults. We examined relationships among PET measures, cortical thickness, and cognition. Results Cortical thickness was reduced in PiB+/FTP+ participants compared to the PiB+/FTP- and PiB-/FTP- groups. Continuous PiB associations with cortical thickness were weak but positive in FTP- participants and negative in FTP+. FTP strongly negatively predicted thickness regardless of PiB status. FTP was associated with memory and cortical thickness, and mediated the association of PiB with memory. Discussion Past findings linking A beta and cortical thickness are likely weak due to opposing effects of A beta on cortical thickness relative to tau burden. Tau, in contrast to A beta, is strongly related to cortical thickness and memory.