Study on transmission of Abeta aggregates and its prevention
| Project/Area Number |
17H04194
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
濱口 毅 金沢大学, 医学系, 准教授 (70452109)
坂井 健二 金沢大学, 附属病院, 講師 (00572306)
池田 篤平 金沢大学, 医学系, 協力研究員 (30755773)
中山 隆宏 金沢大学, ナノ生命科学研究所, 准教授 (00532821)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
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| Keywords | アルツハイマー病 / アミロイドβ蛋白 / 伝播 / 防御 / 凝集 / オートクレーブ処理 / γ線照射 / アミロイドβタンパク |
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| Outline of Final Research Achievements |
Studies with thioflavin T (ThT) assays and high-speed atomic force microscopy revealed that seeding effect of amyloid β-protein (Aβ) aggregates was inactivated by autoclave (AC), depending on different temperatures, exposure times, and concentrations of Aβ aggregates at the treatment with AC. Seeding activity of Aβ40 aggregates was more easily inactivated by AC at the same conditions compared to that of Aβ42 aggregates. Results of ThT fluorescence and circular dichroism spectral patterns of autoclaved Aβ aggregates indicated that AC reduced β-sheet-rich structures in Aβ aggregates. Electron microscopy images demonstrated that lengths of autoclaved Aβ aggregates with fibril-like structures was significantly shorter than those of non-treated ones. Gamma-ray irradiation for Aβ aggregates did not inactivate Aβ seeding effect or induce structural changes of Aβ aggregates significantly.
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| Academic Significance and Societal Importance of the Research Achievements |
アルツハイマー病の中心的病理所見の1つである老人斑を構成するアミロイドβ蛋白（Aβ）は、動物実験レベルで個体間を伝播することが明らかになっている。また、硬膜移植やヒト下垂体由来成長ホルモン製剤投与といった医療行為を介してAβ病理が個体間を伝播し、時間を経て症候性の脳アミロイドアンギオパチー関連脳出血を引き起こす可能性も示唆されている。本研究では、オートクレーブ（AC）がAβ凝集体のβシート構造を減少させ、seeding効果を低下させることを明らかにした。この結果は、ACがAβ凝集体の個体間伝播を予防しうる可能性を示唆し、本研究成果はAβ凝集体の個体間伝播を抑制する不活化法の開発につながる。
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Report
(5 results)
Research Products
(49 results)
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[Journal Article] Costs and resource use associated with community-dwelling patients with Alzheimer's disease in Japan: baseline results from the prospective observational GERAS-J study.2020
Author(s)
Nakanishi M, Igarashi A, Ueda K, Brnabic AJM, Treuer T, Sato M, Kahle-Wrobleski K, Meguro K, Yamada M, Mimura M, Arai H.
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Journal Title
Journal of Alzheimer's Disease
Volume: 74
Pages: 127-138
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Study design and baseline characteristics of a population-based prospective cohort study of dementia in Japan: the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD).2020
Author(s)
Ninomiya T, Nakaji S, Maeda T, Yamada M, Mimura M, Nakashima K, Mori T, Takebayashi M, Ohara T, Hata J, Kokubo Y, Uchida K, Taki Y, Kumagai S, Yonemoto K, Yoshida H, Muto K, Momozawa Y, Akiyama M, Kubo M, Ikeda M, Kanba S, Kiyohara Y.
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Journal Title
Environ Health Prev Med
Volume: 25
Issue: 1
Pages: 64-64
DOI
NAID
ISSN
1342-078X, 1347-4715
Related Report
Peer Reviewed / Open Access
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[Journal Article] Characterization of “sporadic CJD” with history of neurosurgery to identify potentially iatrogenic cases.2020
Author(s)
Hamaguchi T, Sakai K, Kobayashi A, Kitamoto T, Ae R, Nakamura Y, Sanjo N, Arai K, Koide M, Katada F, Harada M, Murai H, Murayama S, Tsukamoto T, Mizusawa H, Yamada M.
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Journal Title
Emerg Infect Dis
Volume: in press
Related Report
Peer Reviewed
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[Presentation] Iatrogenic Creutzfeldt-Jakob disease related to dura mater grafts2017
Author(s)
Yamada M, Hamaguchi T, Sakai K, Noguchi-Shinohara M, Nozaki I, Taniguchi Y, Kobayashi A, Takeuchi A, Kitamoto T, Nakamura Y, Sanjo N, Tsukamoto T, Takao M, Murayama S, Iwasaki Y, Yoshida M, Shimizu H, Kakita A, Takahashi H, Suzuki H, Naiki H, Mizusawa H
Organizer
PRION2017
Related Report
Int'l Joint Research / Invited
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[Presentation] Possible human-to-human transmission of cerebral β-amyloidosis via cadaveric dura mater grafting2017
Author(s)
Yamada M, Hamaguchi T, Taniguchi Y, Sakai K, Kitamoto T, Takao M, Murayama S, Iwasaki Y, Yoshida M, Shimizu H, Kakita A, Takahashi H, Suzuki H, Naiki H, Sanjo N, Mizusawa H
Organizer
Alzheimer's Association International Conference (AAIC) 2017
Related Report
Int'l Joint Research
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