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

## TL;DR

This study examines Alzheimer's patients who have amyloid buildup but no detectable tau protein in brain scans, finding they have milder symptoms and slower progression.

## Contribution

The study introduces the FDA-approved VR method for tau-PET analysis and characterizes a heterogeneous subgroup of AD patients with Aβ positivity but no detectable tau accumulation.

## Key findings

- AD A+T− patients are older and show less hippocampal atrophy and slower cognitive decline compared to AD A+T+.
- AD A+T− patients show higher early-stage tau binding compared to controls but no evidence of tau accumulation over time.
- The AD A+T− group is likely heterogeneous with no consistent co-pathologies or tau accumulation.

## Abstract

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.

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.