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Tau pathology associates with in vivo cortical thinning in Lewy body disorders

OBJECTIVES: To investigate the impact of Alzheimer’s disease (AD) co‐pathology on an in vivo structural measure of neurodegeneration in Lewy body disorders (LBD). METHODS: We studied 72 LBD patients (Parkinson disease (PD) = 2, PD‐MCI = 25, PD with dementia = 10, dementia with Lewy bodies = 35) with...

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Autores principales: Spotorno, Nicola, Coughlin, David G., Olm, Christopher A., Wolk, David, Vaishnavi, Sanjeev N., Shaw, Leslie M., Dahodwala, Nabila, Morley, James F., Duda, John E., Deik, Andres F., Spindler, Meredith A., Chen‐Plotkin, Alice, Lee, Edward B., Trojanowski, John Q., McMillan, Corey T., Weintraub, Daniel, Grossman, Murray, Irwin, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732256/
https://www.ncbi.nlm.nih.gov/pubmed/33108692
http://dx.doi.org/10.1002/acn3.51183
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author Spotorno, Nicola
Coughlin, David G.
Olm, Christopher A.
Wolk, David
Vaishnavi, Sanjeev N.
Shaw, Leslie M.
Dahodwala, Nabila
Morley, James F.
Duda, John E.
Deik, Andres F.
Spindler, Meredith A.
Chen‐Plotkin, Alice
Lee, Edward B.
Trojanowski, John Q.
McMillan, Corey T.
Weintraub, Daniel
Grossman, Murray
Irwin, David J.
author_facet Spotorno, Nicola
Coughlin, David G.
Olm, Christopher A.
Wolk, David
Vaishnavi, Sanjeev N.
Shaw, Leslie M.
Dahodwala, Nabila
Morley, James F.
Duda, John E.
Deik, Andres F.
Spindler, Meredith A.
Chen‐Plotkin, Alice
Lee, Edward B.
Trojanowski, John Q.
McMillan, Corey T.
Weintraub, Daniel
Grossman, Murray
Irwin, David J.
author_sort Spotorno, Nicola
collection PubMed
description OBJECTIVES: To investigate the impact of Alzheimer’s disease (AD) co‐pathology on an in vivo structural measure of neurodegeneration in Lewy body disorders (LBD). METHODS: We studied 72 LBD patients (Parkinson disease (PD) = 2, PD‐MCI = 25, PD with dementia = 10, dementia with Lewy bodies = 35) with either CSF analysis or neuropathological examination and structural MRI during life. The cohort was divided into those harboring significant AD co‐pathology, either at autopsy (intermediate/high AD neuropathologic change) or with CSF signature indicating AD co‐pathology (t‐tau/Aβ (1‐42) > 0.3) (LBD+AD, N = 19), and those without AD co‐pathology (LBD−AD, N = 53). We also included a reference group of 25 patients with CSF biomarker‐confirmed amnestic AD. We investigated differences in MRI cortical thickness estimates between groups, and in the 21 autopsied LBD patients (LBD−AD = 14, LBD+AD = 7), directly tested the association between antemortem MRI and post‐mortem burdens of tau, Aβ, and alpha‐synuclein using digital histopathology in five representative neocortical regions. RESULTS: The LBD+AD group was characterized by cortical thinning in anterior/medial and lateral temporal regions (P < 0.05 FWE‐corrected) relative to LBD−AD. In LBD+AD, cortical thinning was most pronounced in temporal neocortex, whereas the AD reference group showed atrophy that equally encompassed temporal, parietal and frontal neocortex. In autopsied LBD, we found an inverse correlation with cortical thickness and post‐mortem tau pathology, while cortical thickness was not significantly associated with Aβ or alpha‐synuclein pathology. INTERPRETATION: LBD+AD is characterized by temporal neocortical thinning on MRI, and cortical thinning directly correlated with post‐mortem histopathologic burden of tau, suggesting that tau pathology influences the pattern of neurodegeneration in LBD.
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spelling pubmed-77322562020-12-16 Tau pathology associates with in vivo cortical thinning in Lewy body disorders Spotorno, Nicola Coughlin, David G. Olm, Christopher A. Wolk, David Vaishnavi, Sanjeev N. Shaw, Leslie M. Dahodwala, Nabila Morley, James F. Duda, John E. Deik, Andres F. Spindler, Meredith A. Chen‐Plotkin, Alice Lee, Edward B. Trojanowski, John Q. McMillan, Corey T. Weintraub, Daniel Grossman, Murray Irwin, David J. Ann Clin Transl Neurol Research Articles OBJECTIVES: To investigate the impact of Alzheimer’s disease (AD) co‐pathology on an in vivo structural measure of neurodegeneration in Lewy body disorders (LBD). METHODS: We studied 72 LBD patients (Parkinson disease (PD) = 2, PD‐MCI = 25, PD with dementia = 10, dementia with Lewy bodies = 35) with either CSF analysis or neuropathological examination and structural MRI during life. The cohort was divided into those harboring significant AD co‐pathology, either at autopsy (intermediate/high AD neuropathologic change) or with CSF signature indicating AD co‐pathology (t‐tau/Aβ (1‐42) > 0.3) (LBD+AD, N = 19), and those without AD co‐pathology (LBD−AD, N = 53). We also included a reference group of 25 patients with CSF biomarker‐confirmed amnestic AD. We investigated differences in MRI cortical thickness estimates between groups, and in the 21 autopsied LBD patients (LBD−AD = 14, LBD+AD = 7), directly tested the association between antemortem MRI and post‐mortem burdens of tau, Aβ, and alpha‐synuclein using digital histopathology in five representative neocortical regions. RESULTS: The LBD+AD group was characterized by cortical thinning in anterior/medial and lateral temporal regions (P < 0.05 FWE‐corrected) relative to LBD−AD. In LBD+AD, cortical thinning was most pronounced in temporal neocortex, whereas the AD reference group showed atrophy that equally encompassed temporal, parietal and frontal neocortex. In autopsied LBD, we found an inverse correlation with cortical thickness and post‐mortem tau pathology, while cortical thickness was not significantly associated with Aβ or alpha‐synuclein pathology. INTERPRETATION: LBD+AD is characterized by temporal neocortical thinning on MRI, and cortical thinning directly correlated with post‐mortem histopathologic burden of tau, suggesting that tau pathology influences the pattern of neurodegeneration in LBD. John Wiley and Sons Inc. 2020-10-27 /pmc/articles/PMC7732256/ /pubmed/33108692 http://dx.doi.org/10.1002/acn3.51183 Text en © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Spotorno, Nicola
Coughlin, David G.
Olm, Christopher A.
Wolk, David
Vaishnavi, Sanjeev N.
Shaw, Leslie M.
Dahodwala, Nabila
Morley, James F.
Duda, John E.
Deik, Andres F.
Spindler, Meredith A.
Chen‐Plotkin, Alice
Lee, Edward B.
Trojanowski, John Q.
McMillan, Corey T.
Weintraub, Daniel
Grossman, Murray
Irwin, David J.
Tau pathology associates with in vivo cortical thinning in Lewy body disorders
title Tau pathology associates with in vivo cortical thinning in Lewy body disorders
title_full Tau pathology associates with in vivo cortical thinning in Lewy body disorders
title_fullStr Tau pathology associates with in vivo cortical thinning in Lewy body disorders
title_full_unstemmed Tau pathology associates with in vivo cortical thinning in Lewy body disorders
title_short Tau pathology associates with in vivo cortical thinning in Lewy body disorders
title_sort tau pathology associates with in vivo cortical thinning in lewy body disorders
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732256/
https://www.ncbi.nlm.nih.gov/pubmed/33108692
http://dx.doi.org/10.1002/acn3.51183
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