Cerebral hypoperfusion reduces tau accumulation
Abstract Objective Alzheimer's disease (AD) often coexists with cerebrovascular diseases. However, the impact of cerebrovascular diseases such as stroke on AD pathology remains poorly understood. Methods This study examines the correlation between cerebrovascular diseases and AD pathology. The...
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Wiley
2025-01-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.52247 |
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| author | Ghupurjan Gheni Mitsuru Shinohara Masami Masuda‐Suzukake Akihiko Shindo Atsushi Watanabe Kaori Kawai Guojun Bu Hidekazu Tomimoto Masato Hasegawa Naoyuki Sato |
| author_facet | Ghupurjan Gheni Mitsuru Shinohara Masami Masuda‐Suzukake Akihiko Shindo Atsushi Watanabe Kaori Kawai Guojun Bu Hidekazu Tomimoto Masato Hasegawa Naoyuki Sato |
| author_sort | Ghupurjan Gheni |
| collection | DOAJ |
| description | Abstract Objective Alzheimer's disease (AD) often coexists with cerebrovascular diseases. However, the impact of cerebrovascular diseases such as stroke on AD pathology remains poorly understood. Methods This study examines the correlation between cerebrovascular diseases and AD pathology. The research was carried out using clinical and neuropathological data collected from the National Alzheimer's Coordinating Center (NACC) database and an animal model in which bilateral common carotid artery stenosis surgery was performed, following the injection of tau seeds into the brains of wild‐type mice. Results Analysis of the NACC database suggests that clinical stroke history and lacunar infarcts are associated with lower neurofibrillary tangle pathology. An animal model demonstrates that chronic cerebral hypoperfusion reduces tau pathology, which was observed in not only neurons but also astrocytes, microglia, and oligodendrocytes. Furthermore, we found that astrocytes and microglia were activated in response to tau pathology and chronic cerebral hypoperfusion. Additionally, cerebral hypoperfusion increased a lysosomal enzyme, cathepsin D. Interpretation These data together indicate that cerebral hypoperfusion reduces tau accumulation likely through an increase in microglial phagocytic activity towards tau and an elevation in degradation through cathepsin D. This study contributes to understanding the relationship between tau pathology and cerebrovascular diseases in older people with multimorbidity. |
| format | Article |
| id | doaj-art-6049773a35b245058611d234f656004f |
| institution | Kabale University |
| issn | 2328-9503 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj-art-6049773a35b245058611d234f656004f2025-01-21T05:41:42ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-01-01121698510.1002/acn3.52247Cerebral hypoperfusion reduces tau accumulationGhupurjan Gheni0Mitsuru Shinohara1Masami Masuda‐Suzukake2Akihiko Shindo3Atsushi Watanabe4Kaori Kawai5Guojun Bu6Hidekazu Tomimoto7Masato Hasegawa8Naoyuki Sato9Department of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia National Center for Geriatrics and Gerontology 7‐430 Morioka Obu Aichi 474‐8511 JapanDepartment of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia National Center for Geriatrics and Gerontology 7‐430 Morioka Obu Aichi 474‐8511 JapanDementia Research Project Tokyo Metropolitan Institute of Medical Science 2‐1‐6 Kamikitazawa, Setagaya‐ku Tokyo 156‐8506 JapanDepartment of Neurology, Graduate School of Medicine Mie University 1577 Kurima Machiyacho Tsu City Mie 514‐8507 JapanEquipment Management Division, Center for Core Facility Administration, National Center for Geriatrics and Gerontology 7‐430 Morioka Obu Aichi 474‐8511 JapanDepartment of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia National Center for Geriatrics and Gerontology 7‐430 Morioka Obu Aichi 474‐8511 JapanDepartment of Neuroscience Mayo Clinic Jacksonville Florida 32224 USADepartment of Neurology, Graduate School of Medicine Mie University 1577 Kurima Machiyacho Tsu City Mie 514‐8507 JapanDementia Research Project Tokyo Metropolitan Institute of Medical Science 2‐1‐6 Kamikitazawa, Setagaya‐ku Tokyo 156‐8506 JapanDepartment of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia National Center for Geriatrics and Gerontology 7‐430 Morioka Obu Aichi 474‐8511 JapanAbstract Objective Alzheimer's disease (AD) often coexists with cerebrovascular diseases. However, the impact of cerebrovascular diseases such as stroke on AD pathology remains poorly understood. Methods This study examines the correlation between cerebrovascular diseases and AD pathology. The research was carried out using clinical and neuropathological data collected from the National Alzheimer's Coordinating Center (NACC) database and an animal model in which bilateral common carotid artery stenosis surgery was performed, following the injection of tau seeds into the brains of wild‐type mice. Results Analysis of the NACC database suggests that clinical stroke history and lacunar infarcts are associated with lower neurofibrillary tangle pathology. An animal model demonstrates that chronic cerebral hypoperfusion reduces tau pathology, which was observed in not only neurons but also astrocytes, microglia, and oligodendrocytes. Furthermore, we found that astrocytes and microglia were activated in response to tau pathology and chronic cerebral hypoperfusion. Additionally, cerebral hypoperfusion increased a lysosomal enzyme, cathepsin D. Interpretation These data together indicate that cerebral hypoperfusion reduces tau accumulation likely through an increase in microglial phagocytic activity towards tau and an elevation in degradation through cathepsin D. This study contributes to understanding the relationship between tau pathology and cerebrovascular diseases in older people with multimorbidity.https://doi.org/10.1002/acn3.52247 |
| spellingShingle | Ghupurjan Gheni Mitsuru Shinohara Masami Masuda‐Suzukake Akihiko Shindo Atsushi Watanabe Kaori Kawai Guojun Bu Hidekazu Tomimoto Masato Hasegawa Naoyuki Sato Cerebral hypoperfusion reduces tau accumulation Annals of Clinical and Translational Neurology |
| title | Cerebral hypoperfusion reduces tau accumulation |
| title_full | Cerebral hypoperfusion reduces tau accumulation |
| title_fullStr | Cerebral hypoperfusion reduces tau accumulation |
| title_full_unstemmed | Cerebral hypoperfusion reduces tau accumulation |
| title_short | Cerebral hypoperfusion reduces tau accumulation |
| title_sort | cerebral hypoperfusion reduces tau accumulation |
| url | https://doi.org/10.1002/acn3.52247 |
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