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Fabry Disease With Concomitant Lewy Body Disease

Although Gaucher disease can be accompanied by Lewy pathology (LP) and extrapyramidal symptoms, it is unknown if LP exists in Fabry disease (FD), another progressive multisystem lysosomal storage disorder. We aimed to elucidate the distribution patterns of FD-related inclusions and LP in the brain o...

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Autores principales: Del Tredici, Kelly, Ludolph, Albert C, Feldengut, Simone, Jacob, Christian, Reichmann, Heinz, Bohl, Jürgen R, Braak, Heiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092358/
https://www.ncbi.nlm.nih.gov/pubmed/32016321
http://dx.doi.org/10.1093/jnen/nlz139
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author Del Tredici, Kelly
Ludolph, Albert C
Feldengut, Simone
Jacob, Christian
Reichmann, Heinz
Bohl, Jürgen R
Braak, Heiko
author_facet Del Tredici, Kelly
Ludolph, Albert C
Feldengut, Simone
Jacob, Christian
Reichmann, Heinz
Bohl, Jürgen R
Braak, Heiko
author_sort Del Tredici, Kelly
collection PubMed
description Although Gaucher disease can be accompanied by Lewy pathology (LP) and extrapyramidal symptoms, it is unknown if LP exists in Fabry disease (FD), another progressive multisystem lysosomal storage disorder. We aimed to elucidate the distribution patterns of FD-related inclusions and LP in the brain of a 58-year-old cognitively unimpaired male FD patient suffering from predominant hypokinesia. Immunohistochemistry (CD77, α-synuclein, collagen IV) and neuropathological staging were performed on 100-µm sections. Tissue from the enteric or peripheral nervous system was unavailable. As controls, a second cognitively unimpaired 50-year-old male FD patient without LP or motor symptoms and 3 age-matched individuals were examined. Inclusion body pathology was semiquantitatively evaluated. Although Lewy neurites/bodies were not present in the 50-year-old individual or in controls, severe neuronal loss in the substantia nigra pars compacta and LP corresponding to neuropathological stage 4 of Parkinson disease was seen in the 58-year-old FD patient. Major cerebrovascular lesions and/or additional pathologies were absent in this individual. We conclude that Lewy body disease with parkinsonism can occur within the context of FD. Further studies determining the frequencies of both inclusion pathologies in large autopsy-controlled FD cohorts could help clarify the implications of both lesions for disease pathogenesis, potential spreading mechanisms, and therapeutic interventions.
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spelling pubmed-70923582020-03-27 Fabry Disease With Concomitant Lewy Body Disease Del Tredici, Kelly Ludolph, Albert C Feldengut, Simone Jacob, Christian Reichmann, Heinz Bohl, Jürgen R Braak, Heiko J Neuropathol Exp Neurol Original Articles Although Gaucher disease can be accompanied by Lewy pathology (LP) and extrapyramidal symptoms, it is unknown if LP exists in Fabry disease (FD), another progressive multisystem lysosomal storage disorder. We aimed to elucidate the distribution patterns of FD-related inclusions and LP in the brain of a 58-year-old cognitively unimpaired male FD patient suffering from predominant hypokinesia. Immunohistochemistry (CD77, α-synuclein, collagen IV) and neuropathological staging were performed on 100-µm sections. Tissue from the enteric or peripheral nervous system was unavailable. As controls, a second cognitively unimpaired 50-year-old male FD patient without LP or motor symptoms and 3 age-matched individuals were examined. Inclusion body pathology was semiquantitatively evaluated. Although Lewy neurites/bodies were not present in the 50-year-old individual or in controls, severe neuronal loss in the substantia nigra pars compacta and LP corresponding to neuropathological stage 4 of Parkinson disease was seen in the 58-year-old FD patient. Major cerebrovascular lesions and/or additional pathologies were absent in this individual. We conclude that Lewy body disease with parkinsonism can occur within the context of FD. Further studies determining the frequencies of both inclusion pathologies in large autopsy-controlled FD cohorts could help clarify the implications of both lesions for disease pathogenesis, potential spreading mechanisms, and therapeutic interventions. Oxford University Press 2020-04 2019-12-18 /pmc/articles/PMC7092358/ /pubmed/32016321 http://dx.doi.org/10.1093/jnen/nlz139 Text en © 2019 American Association of Neuropathologists, Inc. http://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/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contactjournals.permissions@oup.com
spellingShingle Original Articles
Del Tredici, Kelly
Ludolph, Albert C
Feldengut, Simone
Jacob, Christian
Reichmann, Heinz
Bohl, Jürgen R
Braak, Heiko
Fabry Disease With Concomitant Lewy Body Disease
title Fabry Disease With Concomitant Lewy Body Disease
title_full Fabry Disease With Concomitant Lewy Body Disease
title_fullStr Fabry Disease With Concomitant Lewy Body Disease
title_full_unstemmed Fabry Disease With Concomitant Lewy Body Disease
title_short Fabry Disease With Concomitant Lewy Body Disease
title_sort fabry disease with concomitant lewy body disease
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092358/
https://www.ncbi.nlm.nih.gov/pubmed/32016321
http://dx.doi.org/10.1093/jnen/nlz139
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