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Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure

We describe an autopsied patient with familial parkinsonism and unclassified four repeat-tau (4R-tau) aggregation. She presented with bradykinesia, truncal dystonia, and mild amnesia at the age of 61 and then exhibited body weight loss (15 kg over 8 months), sleep disturbances, and progressive respi...

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Autores principales: Nakano, Masayoshi, Riku, Yuichi, Nishioka, Kenya, Hasegawa, Masato, Washimi, Yukihiko, Arahata, Yutaka, Takeda, Akinori, Horibe, Kentaro, Yamaoka, Akiko, Suzuki, Keisuke, Tsujimoto, Masashi, Li, Yuanzhe, Yoshino, Hiroyo, Hattori, Nobutaka, Akagi, Akio, Miyahara, Hiroaki, Iwasaki, Yasushi, Yoshida, Mari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450700/
https://www.ncbi.nlm.nih.gov/pubmed/32854784
http://dx.doi.org/10.1186/s40478-020-01025-1
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author Nakano, Masayoshi
Riku, Yuichi
Nishioka, Kenya
Hasegawa, Masato
Washimi, Yukihiko
Arahata, Yutaka
Takeda, Akinori
Horibe, Kentaro
Yamaoka, Akiko
Suzuki, Keisuke
Tsujimoto, Masashi
Li, Yuanzhe
Yoshino, Hiroyo
Hattori, Nobutaka
Akagi, Akio
Miyahara, Hiroaki
Iwasaki, Yasushi
Yoshida, Mari
author_facet Nakano, Masayoshi
Riku, Yuichi
Nishioka, Kenya
Hasegawa, Masato
Washimi, Yukihiko
Arahata, Yutaka
Takeda, Akinori
Horibe, Kentaro
Yamaoka, Akiko
Suzuki, Keisuke
Tsujimoto, Masashi
Li, Yuanzhe
Yoshino, Hiroyo
Hattori, Nobutaka
Akagi, Akio
Miyahara, Hiroaki
Iwasaki, Yasushi
Yoshida, Mari
author_sort Nakano, Masayoshi
collection PubMed
description We describe an autopsied patient with familial parkinsonism and unclassified four repeat-tau (4R-tau) aggregation. She presented with bradykinesia, truncal dystonia, and mild amnesia at the age of 61 and then exhibited body weight loss (15 kg over 8 months), sleep disturbances, and progressive respiratory failure with CO(2) narcosis. She died of respiratory failure at the age of 62, 14 months after disease onset. Her brother also showed parkinsonism at the age of 58 and suddenly died 6 months later. Postmortem examination revealed 4R-tau aggregation, which was characterized by neuronal globose-type tangles or pretangles, bush-like or miscellaneous astrocytic inclusions, and coiled bodies. The temporal tip, the striatum, the substantia nigra, the tegmentum of the midbrain, the medullary reticular formation, and the spinal cord were severely involved with tau aggregation. Argyrophilic grains and ballooned neurons were also found in the medial temporal structures, however, extensions of the 4R-aggregations in the case were clearly broader than those of the argyrophilic grains. Western blot analysis of sarkosyl-insoluble fractions from brain lysates revealed prominent bands of tau at both 33 kDa and 37 kDa. Genetic examinations did not reveal any known pathogenic mutations in MAPT, DCTN-1, PSEN-1, or familial or young-onset parkinsonism-related genes. The clinical manifestations, pathologic findings, and biochemical properties of aggregated tau in our patient cannot be explained by argyrophilic grain disease or other known 4R-tauopathies alone. Our results further extend the clinical and neuropathologic spectra of 4R-tauopathy.
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spelling pubmed-74507002020-08-28 Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure Nakano, Masayoshi Riku, Yuichi Nishioka, Kenya Hasegawa, Masato Washimi, Yukihiko Arahata, Yutaka Takeda, Akinori Horibe, Kentaro Yamaoka, Akiko Suzuki, Keisuke Tsujimoto, Masashi Li, Yuanzhe Yoshino, Hiroyo Hattori, Nobutaka Akagi, Akio Miyahara, Hiroaki Iwasaki, Yasushi Yoshida, Mari Acta Neuropathol Commun Case Report We describe an autopsied patient with familial parkinsonism and unclassified four repeat-tau (4R-tau) aggregation. She presented with bradykinesia, truncal dystonia, and mild amnesia at the age of 61 and then exhibited body weight loss (15 kg over 8 months), sleep disturbances, and progressive respiratory failure with CO(2) narcosis. She died of respiratory failure at the age of 62, 14 months after disease onset. Her brother also showed parkinsonism at the age of 58 and suddenly died 6 months later. Postmortem examination revealed 4R-tau aggregation, which was characterized by neuronal globose-type tangles or pretangles, bush-like or miscellaneous astrocytic inclusions, and coiled bodies. The temporal tip, the striatum, the substantia nigra, the tegmentum of the midbrain, the medullary reticular formation, and the spinal cord were severely involved with tau aggregation. Argyrophilic grains and ballooned neurons were also found in the medial temporal structures, however, extensions of the 4R-aggregations in the case were clearly broader than those of the argyrophilic grains. Western blot analysis of sarkosyl-insoluble fractions from brain lysates revealed prominent bands of tau at both 33 kDa and 37 kDa. Genetic examinations did not reveal any known pathogenic mutations in MAPT, DCTN-1, PSEN-1, or familial or young-onset parkinsonism-related genes. The clinical manifestations, pathologic findings, and biochemical properties of aggregated tau in our patient cannot be explained by argyrophilic grain disease or other known 4R-tauopathies alone. Our results further extend the clinical and neuropathologic spectra of 4R-tauopathy. BioMed Central 2020-08-27 /pmc/articles/PMC7450700/ /pubmed/32854784 http://dx.doi.org/10.1186/s40478-020-01025-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Case Report
Nakano, Masayoshi
Riku, Yuichi
Nishioka, Kenya
Hasegawa, Masato
Washimi, Yukihiko
Arahata, Yutaka
Takeda, Akinori
Horibe, Kentaro
Yamaoka, Akiko
Suzuki, Keisuke
Tsujimoto, Masashi
Li, Yuanzhe
Yoshino, Hiroyo
Hattori, Nobutaka
Akagi, Akio
Miyahara, Hiroaki
Iwasaki, Yasushi
Yoshida, Mari
Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure
title Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure
title_full Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure
title_fullStr Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure
title_full_unstemmed Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure
title_short Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure
title_sort unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450700/
https://www.ncbi.nlm.nih.gov/pubmed/32854784
http://dx.doi.org/10.1186/s40478-020-01025-1
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