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Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease (PD). While the clinical presentation of LRRK2 mutation carriers is similar to that of idiopathic PD (iPD) patients, the neuropathology of LRRK2 PD is less clearly defined. Lewy bodies (LBs) c...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858668/ https://www.ncbi.nlm.nih.gov/pubmed/31733655 http://dx.doi.org/10.1186/s40478-019-0836-x |
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author | Henderson, Michael X. Sengupta, Medha Trojanowski, John Q. Lee, Virginia M. Y. |
author_facet | Henderson, Michael X. Sengupta, Medha Trojanowski, John Q. Lee, Virginia M. Y. |
author_sort | Henderson, Michael X. |
collection | PubMed |
description | Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease (PD). While the clinical presentation of LRRK2 mutation carriers is similar to that of idiopathic PD (iPD) patients, the neuropathology of LRRK2 PD is less clearly defined. Lewy bodies (LBs) composed of α-synuclein are a major feature of iPD, but are not present in all LRRK2 PD cases. There is some evidence that tau may act as a neuropathological substrate in LB-negative LRRK2 PD, but this has not been examined systematically. In the current study, we examined α-synuclein, tau, and amyloid β (Aβ) pathologies in 12 LRRK2 mutation carriers. We find that α-synuclein pathology is present in 63.6% of LRRK2 mutation carriers, but tau pathology can be found in 100% of carriers and is abundant in 91% of carriers. We further use an antibody which selectively binds Alzheimer’s disease (AD)-type tau and use quantitative analysis of tau pathology to demonstrate that AD tau is the prominent type of tau present in LRRK2 mutation carriers. Abundant Aβ pathology can also be found in LRRK2 mutation carriers and is consistent with comorbid AD pathology. Finally, we assessed the association of neuropathology with clinical features in LRRK2 mutation carriers and idiopathic individuals and find that LRRK2 PD shares clinical and pathological features of idiopathic PD. The prevalence of AD-type tau pathology in LRRK2 PD is an important consideration for understanding PD pathogenesis and refining clinical trial inclusion and progression criterion. |
format | Online Article Text |
id | pubmed-6858668 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68586682019-11-29 Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease Henderson, Michael X. Sengupta, Medha Trojanowski, John Q. Lee, Virginia M. Y. Acta Neuropathol Commun Research Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease (PD). While the clinical presentation of LRRK2 mutation carriers is similar to that of idiopathic PD (iPD) patients, the neuropathology of LRRK2 PD is less clearly defined. Lewy bodies (LBs) composed of α-synuclein are a major feature of iPD, but are not present in all LRRK2 PD cases. There is some evidence that tau may act as a neuropathological substrate in LB-negative LRRK2 PD, but this has not been examined systematically. In the current study, we examined α-synuclein, tau, and amyloid β (Aβ) pathologies in 12 LRRK2 mutation carriers. We find that α-synuclein pathology is present in 63.6% of LRRK2 mutation carriers, but tau pathology can be found in 100% of carriers and is abundant in 91% of carriers. We further use an antibody which selectively binds Alzheimer’s disease (AD)-type tau and use quantitative analysis of tau pathology to demonstrate that AD tau is the prominent type of tau present in LRRK2 mutation carriers. Abundant Aβ pathology can also be found in LRRK2 mutation carriers and is consistent with comorbid AD pathology. Finally, we assessed the association of neuropathology with clinical features in LRRK2 mutation carriers and idiopathic individuals and find that LRRK2 PD shares clinical and pathological features of idiopathic PD. The prevalence of AD-type tau pathology in LRRK2 PD is an important consideration for understanding PD pathogenesis and refining clinical trial inclusion and progression criterion. BioMed Central 2019-11-16 /pmc/articles/PMC6858668/ /pubmed/31733655 http://dx.doi.org/10.1186/s40478-019-0836-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Henderson, Michael X. Sengupta, Medha Trojanowski, John Q. Lee, Virginia M. Y. Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease |
title | Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease |
title_full | Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease |
title_fullStr | Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease |
title_full_unstemmed | Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease |
title_short | Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease |
title_sort | alzheimer’s disease tau is a prominent pathology in lrrk2 parkinson’s disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858668/ https://www.ncbi.nlm.nih.gov/pubmed/31733655 http://dx.doi.org/10.1186/s40478-019-0836-x |
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