[18F]AV-1451 binding is increased in frontotemporal dementia due to C9orf72 expansion.

The PET ligand [18F]AV-1451 was developed to bind tau pathology in Alzheimer's disease, but increased binding has been shown in both genetic tauopathies and in semantic dementia, a disease strongly associated with TDP-43 pathology. Here we assessed [18F]AV-1451 binding in behavioral variant frontotemporal dementia due to a hexanucleotide repeat expansion in C9orf72, characterized by TDP-43 pathology. We show that the C9orf72 mutation increases binding in frontotemporal cortex, with a distinctive distribution of binding compared with healthy controls.

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

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.