Cargando…

Discriminatory ability of next-generation tau PET tracers for Alzheimer’s disease

A next generation of tau PET tracers for the imaging of Alzheimer’s disease and other dementias has recently been developed. Whilst the new compounds have now entered clinical studies, there is limited information available to assess their suitability for clinical applications. Head-to-head comparis...

Descripción completa

Detalles Bibliográficos
Autores principales: Yap, Steven Y, Frias, Barbara, Wren, Melissa C, Schöll, Michael, Fox, Nick C, Årstad, Erik, Lashley, Tammaryn, Sander, Kerstin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453387/
https://www.ncbi.nlm.nih.gov/pubmed/33742656
http://dx.doi.org/10.1093/brain/awab120
_version_ 1784570263602462720
author Yap, Steven Y
Frias, Barbara
Wren, Melissa C
Schöll, Michael
Fox, Nick C
Årstad, Erik
Lashley, Tammaryn
Sander, Kerstin
author_facet Yap, Steven Y
Frias, Barbara
Wren, Melissa C
Schöll, Michael
Fox, Nick C
Årstad, Erik
Lashley, Tammaryn
Sander, Kerstin
author_sort Yap, Steven Y
collection PubMed
description A next generation of tau PET tracers for the imaging of Alzheimer’s disease and other dementias has recently been developed. Whilst the new compounds have now entered clinical studies, there is limited information available to assess their suitability for clinical applications. Head-to-head comparisons are urgently needed to understand differences in the radiotracer binding profiles. We characterized the binding of the tau tracers PI2620, RO948, MK6240 and JNJ067 in human post-mortem brain tissue from a cohort of 25 dementia cases and age-matched controls using quantitative phosphorimaging with tritium-labelled radiotracers in conjunction with phospho-tau specific immunohistochemistry. The four radiotracers depicted tau inclusions composed of paired helical filaments with high specificity, both in cases with Alzheimer’s disease and in primary tauopathy cases with concomitant Alzheimer’s disease pathology. In contrast, cortical binding to primary tauopathy in cases without paired helical filament tau was found to be within the range of age-matched controls. Off-target binding to monoamine oxidase B has been overcome, as demonstrated by heterologous blocking studies in basal ganglia tissue. The high variability of cortical tracer binding within the Alzheimer’s disease group followed the same pattern with each tracer, suggesting that all compounds are suited to differentiate Alzheimer’s disease from other dementias.
format Online
Article
Text
id pubmed-8453387
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-84533872021-09-22 Discriminatory ability of next-generation tau PET tracers for Alzheimer’s disease Yap, Steven Y Frias, Barbara Wren, Melissa C Schöll, Michael Fox, Nick C Årstad, Erik Lashley, Tammaryn Sander, Kerstin Brain Reports A next generation of tau PET tracers for the imaging of Alzheimer’s disease and other dementias has recently been developed. Whilst the new compounds have now entered clinical studies, there is limited information available to assess their suitability for clinical applications. Head-to-head comparisons are urgently needed to understand differences in the radiotracer binding profiles. We characterized the binding of the tau tracers PI2620, RO948, MK6240 and JNJ067 in human post-mortem brain tissue from a cohort of 25 dementia cases and age-matched controls using quantitative phosphorimaging with tritium-labelled radiotracers in conjunction with phospho-tau specific immunohistochemistry. The four radiotracers depicted tau inclusions composed of paired helical filaments with high specificity, both in cases with Alzheimer’s disease and in primary tauopathy cases with concomitant Alzheimer’s disease pathology. In contrast, cortical binding to primary tauopathy in cases without paired helical filament tau was found to be within the range of age-matched controls. Off-target binding to monoamine oxidase B has been overcome, as demonstrated by heterologous blocking studies in basal ganglia tissue. The high variability of cortical tracer binding within the Alzheimer’s disease group followed the same pattern with each tracer, suggesting that all compounds are suited to differentiate Alzheimer’s disease from other dementias. Oxford University Press 2021-03-20 /pmc/articles/PMC8453387/ /pubmed/33742656 http://dx.doi.org/10.1093/brain/awab120 Text en © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Reports
Yap, Steven Y
Frias, Barbara
Wren, Melissa C
Schöll, Michael
Fox, Nick C
Årstad, Erik
Lashley, Tammaryn
Sander, Kerstin
Discriminatory ability of next-generation tau PET tracers for Alzheimer’s disease
title Discriminatory ability of next-generation tau PET tracers for Alzheimer’s disease
title_full Discriminatory ability of next-generation tau PET tracers for Alzheimer’s disease
title_fullStr Discriminatory ability of next-generation tau PET tracers for Alzheimer’s disease
title_full_unstemmed Discriminatory ability of next-generation tau PET tracers for Alzheimer’s disease
title_short Discriminatory ability of next-generation tau PET tracers for Alzheimer’s disease
title_sort discriminatory ability of next-generation tau pet tracers for alzheimer’s disease
topic Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453387/
https://www.ncbi.nlm.nih.gov/pubmed/33742656
http://dx.doi.org/10.1093/brain/awab120
work_keys_str_mv AT yapsteveny discriminatoryabilityofnextgenerationtaupettracersforalzheimersdisease
AT friasbarbara discriminatoryabilityofnextgenerationtaupettracersforalzheimersdisease
AT wrenmelissac discriminatoryabilityofnextgenerationtaupettracersforalzheimersdisease
AT schollmichael discriminatoryabilityofnextgenerationtaupettracersforalzheimersdisease
AT foxnickc discriminatoryabilityofnextgenerationtaupettracersforalzheimersdisease
AT arstaderik discriminatoryabilityofnextgenerationtaupettracersforalzheimersdisease
AT lashleytammaryn discriminatoryabilityofnextgenerationtaupettracersforalzheimersdisease
AT sanderkerstin discriminatoryabilityofnextgenerationtaupettracersforalzheimersdisease