ArticleActa neuropathologica2026
Disentangling on and off-target binding in flortaucipir PET: a voxel-to-voxel P-tau, ferric iron, and MAO-B histology-to-flortaucipir PET comparison.
Article in Acta neuropathologica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Article
- Genetic Determinants of Tau-PET Imaging in Alzheimer's Disease: A Narrative Review of Genome-Wide and Candidate-Gene Studies.Journal of imaging · 2026Review
- Neocortical tau burden determines the degree of cognitive impairment in individuals with Braak stage V neurofibrillary degeneration.Acta neuropathologica · 2026Article
- Correlation between in vivoAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
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Authors and funding
12 authors.
Funding
Abstract
Flortaucipir PET imaging has significantly advanced our ability to visualize tau pathology in vivo. However, off-target Flortaucipir signal remains a considerable challenge for interpreting of imaging results, particularly in non-Alzheimer's tauopathies and non-tau pathologies. To better understand this off-target signal, we used an innovative voxel-to-voxel correlation approach, analyzing thousands of histology-Flortaucipir pairs from individual cases. This allowed us to quantitatively assess the relationship between Flortaucipir PET signal and three key biological factors: histological tau burden (CP-13 phospho-tau), ferric iron (Perls' Prussian blue), and monoamine oxidase B (MAO-B). Our study included individuals with Alzheimer's disease (AD), various non-AD tauopathies, and a case of FTLD-TDP-43 type A. In AD, Flortaucipir signal showed a significant but moderate correlation with histological tau pathology, suggesting that while tau is a major contributor, other biological factors also influence Flortaucipir binding in AD. Conversely, in non-AD tauopathies and FTLD-TDP-43, correlations between Flortaucipir signal and tau pathology were weak or negligible. Instead, Flortaucipir signal correlated more strongly with ferric iron and MAO-B. However, these factors did not fully explain all the off-target signals, implying other unknown contributors are likely involved. These findings underscore the complexity of interpreting Flortaucipir PET scans. A thorough understanding of off-target binding mechanisms is crucial for improving the diagnostic accuracy of Flortaucipir PET and its specificity.
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