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Alzheimer's Imaging Consortium.

Jeffrey S Phillips1, Amanda E Denning2, Lisa M Levorse2

  • 1Penn Frontotemporal Degeneration Center, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
PubMed
Summary
This summary is machine-generated.

18F-Flortaucipir PET imaging shows sensitivity to Alzheimer's disease tau tangles in early Braak stages. This tau PET tracer primarily reflects neurofibrillary tangles, not thread-like tau inclusions.

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Area of Science:

  • Neuroimaging
  • Neuropathology
  • Alzheimer's Disease Research

Background:

  • 18F-Flortaucipir positron emission tomography (PET) is used for Alzheimer's disease (AD) tau imaging.
  • Concerns exist regarding its sensitivity in early Braak stages and potential off-target binding in the hippocampus.

Purpose of the Study:

  • To investigate the association between antemortem 18F-Flortaucipir PET uptake and postmortem quantified tau and TDP-43 neuropathology.
  • To assess the tracer's sensitivity to early-stage tau pathology.

Main Methods:

  • Used Automated Segmentation of Hippocampal Subfields T1 MRI to segment brain regions.
  • Quantified tau tangles/threads and pTDP-43 inclusions using digital imaging and weakly supervised learning (Wildcat).
  • Computed correlations between 18F-Flortaucipir standardized uptake value ratios (SUVRs) and quantified pathologies.

Main Results:

  • 18F-Flortaucipir SUVRs in the transentorhinal cortex (BA35/36) correlated with neurofibrillary tangles (Spearman's r=0.59, p=0.029).
  • Hippocampal tangle burden correlated with SUVRs in both anterior and posterior hippocampus (r=0.77, p=0.002).
  • PET SUVRs did not associate with somatic or neuritic pTDP-43 measures.

Conclusions:

  • 18F-Flortaucipir demonstrates sensitivity to tau burden in regions relevant to early Braak stages.
  • The tracer primarily reflects neurofibrillary tangles, distinguishing them from tau threads.