Imaging tau pathology in Parkinsonisms

Abstract The recent development of positron emission tomography radiotracers targeting pathological tau in vivo has led to numerous human trials. While investigations have primarily focused on the most common tauopathy, Alzheimer’s disease, it is imperative that testing also be performed in parkinso...

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Main Authors: Sarah Coakeley, Antonio P. Strafella
Format: Article
Language:English
Published: Nature Portfolio 2017-06-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-017-0023-3
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author Sarah Coakeley
Antonio P. Strafella
author_facet Sarah Coakeley
Antonio P. Strafella
author_sort Sarah Coakeley
collection DOAJ
description Abstract The recent development of positron emission tomography radiotracers targeting pathological tau in vivo has led to numerous human trials. While investigations have primarily focused on the most common tauopathy, Alzheimer’s disease, it is imperative that testing also be performed in parkinsonian tauopathies, such as progressive supranuclear palsy, corticobasal degeneration, and frontotemporal dementia and parkinsonism linked to chromosome 17. Tau aggregates differ in isoforms and conformations across disorders, and as a result one radiotracer may not be appropriate for all tauopathies. In this review, we evaluate the preclinical and clinical reports of current tau radiotracers in parkinsonian disorders. These radiotracers include [18F]FDDNP, [11C]PBB3, [18F]THK-5317, [18F]THK-5351, and [18F]AV-1451 ([18F]T807). There are concerns of off-target binding with [18F]FDDNP and [11C]PBB3, which may increase the signal to noise ratio and thereby decrease the efficacy of these radiotracers. Testing in [18F]THK-5317, [18F]THK-5351, and [18F]AV-1451 has been performed in progressive supranuclear palsy, while [18F]THK-5317 and [18F]AV-1451 have also been tested in corticobasal degeneration patients. [18F]THK-5317 and [18F]THK-5351 have demonstrated binding in brain regions known to be afflicted with pathological tau; however, due to small sample sizes these studies should be replicated before concluding their appropriateness in parkinsonian tauopathies. [18F]AV-1451 has demonstrated mixed results in progressive supranuclear palsy patients and post-mortem analysis shows minimal to no binding to non-Alzheimer’s disease tauopathies brain slices.
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spelling doaj.art-6afea461ad4e4fbcb28d678c014008db2023-12-03T03:38:32ZengNature Portfolionpj Parkinson's Disease2373-80572017-06-01311910.1038/s41531-017-0023-3Imaging tau pathology in ParkinsonismsSarah Coakeley0Antonio P. Strafella1Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of TorontoResearch Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of TorontoAbstract The recent development of positron emission tomography radiotracers targeting pathological tau in vivo has led to numerous human trials. While investigations have primarily focused on the most common tauopathy, Alzheimer’s disease, it is imperative that testing also be performed in parkinsonian tauopathies, such as progressive supranuclear palsy, corticobasal degeneration, and frontotemporal dementia and parkinsonism linked to chromosome 17. Tau aggregates differ in isoforms and conformations across disorders, and as a result one radiotracer may not be appropriate for all tauopathies. In this review, we evaluate the preclinical and clinical reports of current tau radiotracers in parkinsonian disorders. These radiotracers include [18F]FDDNP, [11C]PBB3, [18F]THK-5317, [18F]THK-5351, and [18F]AV-1451 ([18F]T807). There are concerns of off-target binding with [18F]FDDNP and [11C]PBB3, which may increase the signal to noise ratio and thereby decrease the efficacy of these radiotracers. Testing in [18F]THK-5317, [18F]THK-5351, and [18F]AV-1451 has been performed in progressive supranuclear palsy, while [18F]THK-5317 and [18F]AV-1451 have also been tested in corticobasal degeneration patients. [18F]THK-5317 and [18F]THK-5351 have demonstrated binding in brain regions known to be afflicted with pathological tau; however, due to small sample sizes these studies should be replicated before concluding their appropriateness in parkinsonian tauopathies. [18F]AV-1451 has demonstrated mixed results in progressive supranuclear palsy patients and post-mortem analysis shows minimal to no binding to non-Alzheimer’s disease tauopathies brain slices.https://doi.org/10.1038/s41531-017-0023-3
spellingShingle Sarah Coakeley
Antonio P. Strafella
Imaging tau pathology in Parkinsonisms
npj Parkinson's Disease
title Imaging tau pathology in Parkinsonisms
title_full Imaging tau pathology in Parkinsonisms
title_fullStr Imaging tau pathology in Parkinsonisms
title_full_unstemmed Imaging tau pathology in Parkinsonisms
title_short Imaging tau pathology in Parkinsonisms
title_sort imaging tau pathology in parkinsonisms
url https://doi.org/10.1038/s41531-017-0023-3
work_keys_str_mv AT sarahcoakeley imagingtaupathologyinparkinsonisms
AT antoniopstrafella imagingtaupathologyinparkinsonisms