A study on transmission of cerebral beta-amyloidosis via dura mater grafting using Alzheimer's disease model mice

• Project/Area Number: 17K09752
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kanazawa University
• Principal Investigator: Hamaguchi Tsuyoshi 金沢大学, 附属病院, 講師 (70452109)
• Co-Investigator(Kenkyū-buntansha): 山田 正仁 金沢大学, 医学系, 教授 (80191336)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アルツハイマー病 / 硬膜移植 / プリオン / プリオン病 / 医原性 / 伝播

Outline of Final Research Achievements

We obtained dura maters from 33 autopsied patients from a geriatric brain bank, and immunohistochemical study of those dura maters were performed using an antibody against amyloid beta protein (Abeta). Eight of 33 patients (24.2%) had Abeta deposition on the vessel of the dura mater. The dura maters were homogenized at 19% (w/v) in PBS, and the supernatants were injected into the brain of Alzheimer’s disease (AD) model mice. One year after the injection, immunohistochemical study using the antibody against Abeta showed that Abeta deposited on the vessels of AD model mice brain injected the homogenate of dura mater with Abeta deposition, while no Abeta deposition was observed in the brain and vessels of AD model mice injected the homogenate of dura mater without Abeta deposition.

Academic Significance and Societal Importance of the Research Achievements

ヒト硬膜にAbeta沈着を認めることを示し、更にその硬膜上のAbetaを脳内に接種することによって脳内に接種された側のモデル動物の脳血管へのAbeta沈着を引き起こすことを証明した。このことは硬膜移植が脳のAbeta病理の個体間伝播の原因となることを直接証明しており、これまでのヒト剖検脳を用いた観察研究の結果を支持する結果である。1980年代には、わが国では年間200000件の硬膜移植が行われていた事が知られており、硬膜移植によって脳へのAbeta病理が伝播することが証明された意義は大きい。

Research Products

• [Journal Article] Acquired cerebral amyloid angiopathy: An emerging concept (2019)
  • Author(s): Yamada Masahito、Hamaguchi Tsuyoshi、Sakai Kenji
  • Journal Title: Prog Mol Biol Transl Sci Volume: 168 Pages: 85-95
  • DOI: 10.1016/bs.pmbts.2019.05.012
  • Peer Reviewed
• [Journal Article] Cerebral hemorrhagic stroke associated with cerebral amyloid angiopathy in young adults about 3 decades after neurosurgeries in their infancy. (2019)
  • Author(s): Hamaguchi T, Komatsu J, Sakai K, Noguchi-Shinohara M, Aoki S, Ikeuchi T, Yamada M
  • Journal Title: J Neurol Sci Volume: 399 Pages: 3-5
  • DOI: 10.1016/j.jns.2019.01.051
  • Peer Reviewed
• [Journal Article] Neuronal intranuclear inclusion disease showing blepharoptosis and positive serum anti-acetylcholine receptor antibody without myasthenia gravis. (2019)
  • Author(s): 1Hayashi K, Hamaguchi T, Sakai K, Nakamura K, Wakabayashi K, Shirasaki H, Yamada M
  • Journal Title: J Neurol Sci Volume: 400 Pages: 119-121
  • DOI: 10.1016/j.jns.2019.03.013
  • Peer Reviewed
• [Journal Article] Specific amyloid-b42 deposition in the brain of a Gerstmann-Straussler-Scheinker disease patient with a P105L mutation on the prion protein gene. (2018)
  • Author(s): Furukawa F, Sanjo N, Kobayashi A, Hamaguchi T, Yamada M, Kitamoto T, Mizusawa H, Yokota T
  • Journal Title: Prion Volume: 12 Issue: 5-6 Pages: 315-319
  • DOI: 10.1080/19336896.2018.1541689
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The sulfation code for propagation of neurodegeneration (2018)
  • Author(s): Yamada M, Hamaguchi T
  • Journal Title: J Biol Chem Volume: 293 Issue: 27 Pages: 10841-10842
  • DOI: 10.1074/jbc.h118.003970
  • Peer Reviewed / Open Access