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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. Highlights: 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.