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Tau accumulation in the nucleus accumbens in tangle-predominant dementia
BACKGROUND: Tangle-predominant dementia (TPD) is characterized neuropathologically by numerous neurofibrillary tangles in the limbic areas with no or occasional senile plaques throughout the brain. TPD is an under-recognized disease, while it is a common cause of dementia in those over 80 years of a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023632/ https://www.ncbi.nlm.nih.gov/pubmed/24708916 http://dx.doi.org/10.1186/2051-5960-2-40 |
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author | Kawakami, Ito Hasegawa, Masato Arai, Tetsuaki Ikeda, Kenji Oshima, Kenichi Niizato, Kazuhiro Aoki, Naoya Omi, Katsuse Higashi, Shinji Hosokawa, Masato Hirayasu, Yoshio Akiyama, Haruhiko |
author_facet | Kawakami, Ito Hasegawa, Masato Arai, Tetsuaki Ikeda, Kenji Oshima, Kenichi Niizato, Kazuhiro Aoki, Naoya Omi, Katsuse Higashi, Shinji Hosokawa, Masato Hirayasu, Yoshio Akiyama, Haruhiko |
author_sort | Kawakami, Ito |
collection | PubMed |
description | BACKGROUND: Tangle-predominant dementia (TPD) is characterized neuropathologically by numerous neurofibrillary tangles in the limbic areas with no or occasional senile plaques throughout the brain. TPD is an under-recognized disease, while it is a common cause of dementia in those over 80 years of age. In the present study, we describe hyperphosphorylated tau (tau) accumulation in the nucleus accumbens (Acb) in patients with TPD. RESULTS: We investigated immunohistochemically the brain tissues from 7 patients with TPD, 22 with Alzheimer disease (AD) and 11 non-demented aged subjects. In the Acb of all 7 TPD patients, a considerable number of tau positive neurons were found together with many neuropil threads. The tau deposits in the Acb were labeled with all the anti-tau antibodies used in the present study. They included conformational change-specific, phosphorylation-specific and phosphorylation-independent antibodies. The Acb consists of the predominant medium-sized neurons with a small number of large neurons. Both the cell types were affected by tau pathology in TPD. Tau accumulation in the majority of such neurons appeared to be pretangle-like, diffuse deposits with only occasional paired helical filament formation. Tau positive neurons were also found in the Acb in some AD and non-demented aged subjects but much fewer in the majority of cases. The immunoblot analyses of fresh frozen samples of the Acb and parahippocampal cortex from 3 TPD and 3 AD patients revealed that the insoluble tau in the Acb was a mixture of the 3- and 4-repeat isoforms. CONCLUSIONS: To our knowledge, this is the first report on the occurrence of tau accumulation in the Acb in TPD. The Acb receives direct and massive projections from the hippocampal CA1 and subiculum where neurofibrillary tangles are known to occur more frequently in TPD than in AD. The prevalence of abnormal tau accumulation in the Acb in TPD may support the idea that abnormal tau aggregation propagates via neural circuits. In all but one TPD cases used in this study, delusion was a consistent clinical feature. Whether the Acb tau accumulation is related to the psychiatric symptoms in TPD may be an issue for further investigation. |
format | Online Article Text |
id | pubmed-4023632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40236322014-05-16 Tau accumulation in the nucleus accumbens in tangle-predominant dementia Kawakami, Ito Hasegawa, Masato Arai, Tetsuaki Ikeda, Kenji Oshima, Kenichi Niizato, Kazuhiro Aoki, Naoya Omi, Katsuse Higashi, Shinji Hosokawa, Masato Hirayasu, Yoshio Akiyama, Haruhiko Acta Neuropathol Commun Research BACKGROUND: Tangle-predominant dementia (TPD) is characterized neuropathologically by numerous neurofibrillary tangles in the limbic areas with no or occasional senile plaques throughout the brain. TPD is an under-recognized disease, while it is a common cause of dementia in those over 80 years of age. In the present study, we describe hyperphosphorylated tau (tau) accumulation in the nucleus accumbens (Acb) in patients with TPD. RESULTS: We investigated immunohistochemically the brain tissues from 7 patients with TPD, 22 with Alzheimer disease (AD) and 11 non-demented aged subjects. In the Acb of all 7 TPD patients, a considerable number of tau positive neurons were found together with many neuropil threads. The tau deposits in the Acb were labeled with all the anti-tau antibodies used in the present study. They included conformational change-specific, phosphorylation-specific and phosphorylation-independent antibodies. The Acb consists of the predominant medium-sized neurons with a small number of large neurons. Both the cell types were affected by tau pathology in TPD. Tau accumulation in the majority of such neurons appeared to be pretangle-like, diffuse deposits with only occasional paired helical filament formation. Tau positive neurons were also found in the Acb in some AD and non-demented aged subjects but much fewer in the majority of cases. The immunoblot analyses of fresh frozen samples of the Acb and parahippocampal cortex from 3 TPD and 3 AD patients revealed that the insoluble tau in the Acb was a mixture of the 3- and 4-repeat isoforms. CONCLUSIONS: To our knowledge, this is the first report on the occurrence of tau accumulation in the Acb in TPD. The Acb receives direct and massive projections from the hippocampal CA1 and subiculum where neurofibrillary tangles are known to occur more frequently in TPD than in AD. The prevalence of abnormal tau accumulation in the Acb in TPD may support the idea that abnormal tau aggregation propagates via neural circuits. In all but one TPD cases used in this study, delusion was a consistent clinical feature. Whether the Acb tau accumulation is related to the psychiatric symptoms in TPD may be an issue for further investigation. BioMed Central 2014-04-08 /pmc/articles/PMC4023632/ /pubmed/24708916 http://dx.doi.org/10.1186/2051-5960-2-40 Text en Copyright © 2014 Kawakami et al.; licensee BioMed Central Ltd. 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 use, distribution, and reproduction in any medium, provided the original work is properly credited. 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 Kawakami, Ito Hasegawa, Masato Arai, Tetsuaki Ikeda, Kenji Oshima, Kenichi Niizato, Kazuhiro Aoki, Naoya Omi, Katsuse Higashi, Shinji Hosokawa, Masato Hirayasu, Yoshio Akiyama, Haruhiko Tau accumulation in the nucleus accumbens in tangle-predominant dementia |
title | Tau accumulation in the nucleus accumbens in tangle-predominant dementia |
title_full | Tau accumulation in the nucleus accumbens in tangle-predominant dementia |
title_fullStr | Tau accumulation in the nucleus accumbens in tangle-predominant dementia |
title_full_unstemmed | Tau accumulation in the nucleus accumbens in tangle-predominant dementia |
title_short | Tau accumulation in the nucleus accumbens in tangle-predominant dementia |
title_sort | tau accumulation in the nucleus accumbens in tangle-predominant dementia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023632/ https://www.ncbi.nlm.nih.gov/pubmed/24708916 http://dx.doi.org/10.1186/2051-5960-2-40 |
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