Abstract
INTRODUCTION: The deposition of neurofibrillary tangles in neurodegenerative disorders is associated with neuronal loss on autopsy; however, their in vivo associations with atrophy across the continuum of Alzheimer's disease (AD) remain unclear. METHODS: We estimated cortical thickness, tau ([(18)F]-AV-1451), and amyloid β (Aβ) status ([(11)C]-PiB) in 47 subjects who were stratified into Aβ- (14 healthy controls and six mild cognitive impairment-Aβ-) and Aβ+ (14 mild cognitive impairment-Aβ+ and 13 AD) groups. RESULTS: Compared with the Aβ- group, tau was increased in widespread regions whereas cortical thinning was restricted to the temporal cortices. Increased tau binding was associated with cortical thinning in each Aβ group. Locally, regional tau was associated with temporoparietal atrophy. DISCUSSION: These findings position tau as a promising therapeutic target. Further studies are needed to elucidate the casual relationships between tau pathology and trajectories of atrophy in AD.