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(18)F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy

The ability to assess the distribution and extent of tau pathology in Alzheimer’s disease and progressive supranuclear palsy in vivo would help to develop biomarkers for these tauopathies and clinical trials of disease-modifying therapies. New radioligands for positron emission tomography have gener...

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Autores principales: Passamonti, Luca, Vázquez Rodríguez, Patricia, Hong, Young T., Allinson, Kieren S. J., Williamson, David, Borchert, Robin J., Sami, Saber, Cope, Thomas E., Bevan-Jones, W. Richard, Jones, P. Simon, Arnold, Robert, Surendranathan, Ajenthan, Mak, Elijah, Su, Li, Fryer, Tim D., Aigbirhio, Franklin I., O’Brien, John T., Rowe, James B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382948/
https://www.ncbi.nlm.nih.gov/pubmed/28122879
http://dx.doi.org/10.1093/brain/aww340
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author Passamonti, Luca
Vázquez Rodríguez, Patricia
Hong, Young T.
Allinson, Kieren S. J.
Williamson, David
Borchert, Robin J.
Sami, Saber
Cope, Thomas E.
Bevan-Jones, W. Richard
Jones, P. Simon
Arnold, Robert
Surendranathan, Ajenthan
Mak, Elijah
Su, Li
Fryer, Tim D.
Aigbirhio, Franklin I.
O’Brien, John T.
Rowe, James B.
author_facet Passamonti, Luca
Vázquez Rodríguez, Patricia
Hong, Young T.
Allinson, Kieren S. J.
Williamson, David
Borchert, Robin J.
Sami, Saber
Cope, Thomas E.
Bevan-Jones, W. Richard
Jones, P. Simon
Arnold, Robert
Surendranathan, Ajenthan
Mak, Elijah
Su, Li
Fryer, Tim D.
Aigbirhio, Franklin I.
O’Brien, John T.
Rowe, James B.
author_sort Passamonti, Luca
collection PubMed
description The ability to assess the distribution and extent of tau pathology in Alzheimer’s disease and progressive supranuclear palsy in vivo would help to develop biomarkers for these tauopathies and clinical trials of disease-modifying therapies. New radioligands for positron emission tomography have generated considerable interest, and controversy, in their potential as tau biomarkers. We assessed the radiotracer (18)F-AV-1451 with positron emission tomography imaging to compare the distribution and intensity of tau pathology in 15 patients with Alzheimer’s pathology (including amyloid-positive mild cognitive impairment), 19 patients with progressive supranuclear palsy, and 13 age- and sex-matched controls. Regional analysis of variance and a support vector machine were used to compare and discriminate the clinical groups, respectively. We also examined the (18)F-AV-1451 autoradiographic binding in post-mortem tissue from patients with Alzheimer’s disease, progressive supranuclear palsy, and a control case to assess the (18)F-AV-1451 binding specificity to Alzheimer’s and non-Alzheimer’s tau pathology. There was increased (18)F-AV-1451 binding in multiple regions in living patients with Alzheimer’s disease and progressive supranuclear palsy relative to controls [main effect of group, F(2,41) = 17.5, P < 0.0001; region of interest × group interaction, F(2,68) = 7.5, P < 0.00001]. More specifically, (18)F-AV-1451 binding was significantly increased in patients with Alzheimer’s disease, relative to patients with progressive supranuclear palsy and with control subjects, in the hippocampus and in occipital, parietal, temporal, and frontal cortices (t’s > 2.2, P’s < 0.04). Conversely, in patients with progressive supranuclear palsy, relative to patients with Alzheimer’s disease, (18)F-AV-1451 binding was elevated in the midbrain (t = 2.1, P < 0.04); while patients with progressive supranuclear palsy showed, relative to controls, increased (18)F-AV-1451 uptake in the putamen, pallidum, thalamus, midbrain, and in the dentate nucleus of the cerebellum (t’s > 2.7, P’s < 0.02). The support vector machine assigned patients’ diagnoses with 94% accuracy. The post-mortem autoradiographic data showed that (18)F-AV-1451 strongly bound to Alzheimer-related tau pathology, but less specifically in progressive supranuclear palsy. (18)F-AV-1451 binding to the basal ganglia was strong in all groups in vivo. Postmortem histochemical staining showed absence of neuromelanin-containing cells in the basal ganglia, indicating that off-target binding to neuromelanin is an insufficient explanation of (18)F-AV-1451 positron emission tomography data in vivo, at least in the basal ganglia. Overall, we confirm the potential of (18)F-AV-1451 as a heuristic biomarker, but caution is indicated in the neuropathological interpretation of its binding. Off-target binding may contribute to disease profiles of (18)F-AV-1451 positron emission tomography, especially in primary tauopathies such as progressive supranuclear palsy. We suggest that (18)F-AV-1451 positron emission tomography is a useful biomarker to assess tau pathology in Alzheimer’s disease and to distinguish it from other tauopathies with distinct clinical and pathological characteristics such as progressive supranuclear palsy.
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spelling pubmed-53829482017-04-11 (18)F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy Passamonti, Luca Vázquez Rodríguez, Patricia Hong, Young T. Allinson, Kieren S. J. Williamson, David Borchert, Robin J. Sami, Saber Cope, Thomas E. Bevan-Jones, W. Richard Jones, P. Simon Arnold, Robert Surendranathan, Ajenthan Mak, Elijah Su, Li Fryer, Tim D. Aigbirhio, Franklin I. O’Brien, John T. Rowe, James B. Brain Original Articles The ability to assess the distribution and extent of tau pathology in Alzheimer’s disease and progressive supranuclear palsy in vivo would help to develop biomarkers for these tauopathies and clinical trials of disease-modifying therapies. New radioligands for positron emission tomography have generated considerable interest, and controversy, in their potential as tau biomarkers. We assessed the radiotracer (18)F-AV-1451 with positron emission tomography imaging to compare the distribution and intensity of tau pathology in 15 patients with Alzheimer’s pathology (including amyloid-positive mild cognitive impairment), 19 patients with progressive supranuclear palsy, and 13 age- and sex-matched controls. Regional analysis of variance and a support vector machine were used to compare and discriminate the clinical groups, respectively. We also examined the (18)F-AV-1451 autoradiographic binding in post-mortem tissue from patients with Alzheimer’s disease, progressive supranuclear palsy, and a control case to assess the (18)F-AV-1451 binding specificity to Alzheimer’s and non-Alzheimer’s tau pathology. There was increased (18)F-AV-1451 binding in multiple regions in living patients with Alzheimer’s disease and progressive supranuclear palsy relative to controls [main effect of group, F(2,41) = 17.5, P < 0.0001; region of interest × group interaction, F(2,68) = 7.5, P < 0.00001]. More specifically, (18)F-AV-1451 binding was significantly increased in patients with Alzheimer’s disease, relative to patients with progressive supranuclear palsy and with control subjects, in the hippocampus and in occipital, parietal, temporal, and frontal cortices (t’s > 2.2, P’s < 0.04). Conversely, in patients with progressive supranuclear palsy, relative to patients with Alzheimer’s disease, (18)F-AV-1451 binding was elevated in the midbrain (t = 2.1, P < 0.04); while patients with progressive supranuclear palsy showed, relative to controls, increased (18)F-AV-1451 uptake in the putamen, pallidum, thalamus, midbrain, and in the dentate nucleus of the cerebellum (t’s > 2.7, P’s < 0.02). The support vector machine assigned patients’ diagnoses with 94% accuracy. The post-mortem autoradiographic data showed that (18)F-AV-1451 strongly bound to Alzheimer-related tau pathology, but less specifically in progressive supranuclear palsy. (18)F-AV-1451 binding to the basal ganglia was strong in all groups in vivo. Postmortem histochemical staining showed absence of neuromelanin-containing cells in the basal ganglia, indicating that off-target binding to neuromelanin is an insufficient explanation of (18)F-AV-1451 positron emission tomography data in vivo, at least in the basal ganglia. Overall, we confirm the potential of (18)F-AV-1451 as a heuristic biomarker, but caution is indicated in the neuropathological interpretation of its binding. Off-target binding may contribute to disease profiles of (18)F-AV-1451 positron emission tomography, especially in primary tauopathies such as progressive supranuclear palsy. We suggest that (18)F-AV-1451 positron emission tomography is a useful biomarker to assess tau pathology in Alzheimer’s disease and to distinguish it from other tauopathies with distinct clinical and pathological characteristics such as progressive supranuclear palsy. Oxford University Press 2017-03 2017-01-24 /pmc/articles/PMC5382948/ /pubmed/28122879 http://dx.doi.org/10.1093/brain/aww340 Text en © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Passamonti, Luca
Vázquez Rodríguez, Patricia
Hong, Young T.
Allinson, Kieren S. J.
Williamson, David
Borchert, Robin J.
Sami, Saber
Cope, Thomas E.
Bevan-Jones, W. Richard
Jones, P. Simon
Arnold, Robert
Surendranathan, Ajenthan
Mak, Elijah
Su, Li
Fryer, Tim D.
Aigbirhio, Franklin I.
O’Brien, John T.
Rowe, James B.
(18)F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy
title (18)F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy
title_full (18)F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy
title_fullStr (18)F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy
title_full_unstemmed (18)F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy
title_short (18)F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy
title_sort (18)f-av-1451 positron emission tomography in alzheimer’s disease and progressive supranuclear palsy
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382948/
https://www.ncbi.nlm.nih.gov/pubmed/28122879
http://dx.doi.org/10.1093/brain/aww340
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