In vivo coupling of tau pathology and cortical thinning in Alzheimer's disease.

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 ([18F]-AV-1451), and amyloid ß (Aß) status ([11C]-PiB) in 47 subjects who were stratified into Aß- (14 healthy controls and six mild cognitive impairment-Aß-) and Aß+ (14 mild cognitive impairment-Aß+ and 13 AD) groups. RESULTS: Compared with the Aß- 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 Aß 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.