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 [ 18 F]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 [ 18 F]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.