Objective Detection of focal brain tau deposition during life could greatly facilitate accurate diagnosis of Alzheimer’s disease (AD), staging and monitoring of disease progression, and development of disease modifying therapies. Methods We acquired tau positron emission tomography (PET) using 18F T807 (AV1451), and amyloid-β PET using 11C Pittsburgh Compound B (PIB) in older clinically normal individuals, and symptomatic patients with mild cognitive impairment or mild AD dementia. Results We found abnormally high cortical 18F T807 binding in patients with mild cognitive impairment and AD dementia compared to clinically normal controls. Consistent with the neuropathology literature, the presence of elevated neocortical 18F T807 binding particularly in the inferior temporal gyrus was associated with clinical impairment. The association of cognitive impairment was stronger with inferior temporal 18F T807 than with mean cortical 11C PIB. Regional 18F T807 was correlated with mean cortical 11C PiB among both impaired and control subjects. Interpretation These findings suggest that 18F T807 PET could have value as a biomarker that reflects both the progression of AD tauopathy and the emergence of clinical impairment.

Objective To examine region and substrate-specific autoradiographic and in vitro binding patterns of PET tracer [F-18]-AV-1451 (previously known as T807), tailored to allow in vivo detection of paired helical filament tau-containing lesions, and to determine whether there is off-target binding to other amyloid/non-amyloid proteins. Methods We applied [F-18]-AV-1451 phosphor screen autoradiography, [F-18]-AV-1451 nuclear emulsion autoradiography and [H-3]-AV-1451 in vitro binding assays to the study of postmortem samples from patients with a definite pathological diagnosis of Alzheimer’s disease, frontotemporal lobar degeneration-tau, frontotemporal lobar degeneration-TDP-43, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy, cerebral amyloid angiopathy and elderly controls free of pathology. Results Our data suggest that AV-1451 strongly binds to tau lesions primarily made of paired helical filaments in Alzheimer’s brains e.g. intra and extraneuronal tangles and dystrophic neurites, but does not seem to bind to a significant extent to neuronal and glial inclusions mainly composed of straight tau filaments in non-Alzheimer tauopathy brains or to β-amyloid, α-synuclein or TDP-43-containing lesions. AV-1451 off-target binding to neuromelanin- and melanin-containing cells and, to a lesser extent, to brain hemorrhagic lesions was identified. Interpretation Our data suggest that AV-1451 holds promise as surrogate marker for the detection of brain tau pathology in the form of tangles and paired helical filament-tau-containing neurites in Alzheimer’s brains but also point to its relatively lower affinity for lesions primarily made of straight tau filaments in non-Alzheimer tauopathy cases and to the existence of some AV-1451 off-target binding. These findings provide important insights for interpreting in vivo patterns of [F-18]-AV-1451 retention.