Characterizing visual read tau‐PET‐negative participants with Alzheimer's disease dementia

A subset of amyloid beta (Aβ)-positive Alzheimer's disease (AD) patients is tau-positron emission tomography (PET) negative. We aimed to characterize this subgroup using [18F]flortaucipir PET visual read (VR), as this is important for prognosis and selection for therapies. Aβ-positive VR tau-PET-negative AD dementia patients (AD A+T-) were compared to tau-PET-positive AD patients (AD A+T+) and control groups (CU A-T-; CU A+T-) included from the Amsterdam-based cohort and Alzheimer's Disease Neuroimaging Initiative (ADNI). We compared [18F]flortaucipir binding in an early- and late-stage tau ROI, atrophy, cognition, and co-pathologies. AD A+T- were older, showed less hippocampal atrophy and slower cognitive decline compared to AD A+T+. In ADNI, AD A+T- showed higher early-stage tau binding compared to both control groups and more late-stage tau compared to CU A-T-, but no tau accumulation over time. VR tau-PET-negative AD patients show neurodegenerative and cognitive processes consistent with the AD trajectory, but milder progression compared to tau-PET-positive AD patients. We used the novel Food and Drug Administration (FDA)-approved VR method for defining tau-PET positivity. AD A+T- patients were older and showed less atrophy and cognitive decline than AD A+T+. We did not find convincing evidence of tau accumulation in AD A+T- or copathologies. The group of AD A+T- patients is likely very heterogeneous.