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.

We conclude that a history of lifelong cognitive activity may support better cognitive performance by a mechanism that is independent of brain β-amyloid burden, brain glucose metabolism, or hippocampal volume.