Dynamic neuropathological study on CBD and PSP.

• Project/Area Number: 16K09734
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Saito Yuko 国立研究開発法人国立精神・神経医療研究センター, 病院 臨床検査部, 医長 (60344066)
• Research Collaborator: MURAYAMA shigeo
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 臨床神経形態学 / THK 5351 / 病理診断 / 画像病理連関 / タウ / PET / 神経病理 / 皮質基底核変性症 / 進行性核上性麻痺 / タウPET / PSP / タウオパチー / ブレインバンク / 神経科学 / 神経内科 / 神経放射線

Outline of Final Research Achievements

In this study, pathological retrospective examination and imaging and autopsy pathology linkage of tau PET (THK 5351) imaging cases were performed. In retrospect, both PSP and CBD considered that the basal ganglia was appropriate as the region of interest. In this example of PET imaging, it was possible to examine linkage in 2 cases in which the clinical case was frontotemporal dementia and the autopsy diagnosis was CBD, and both the clinical and pathological diagnosis were PSP. The site with strong accumulation of this PET was strong in both tau deposition and degeneration. During the study period, it became clear that this tau PET binds to MAO-B, but there is also a disease that is specific in the site of degeneration, and from that point of view it is considered that there is an active pathway of this PET.

Academic Significance and Societal Importance of the Research Achievements

大脳皮質基底核変性症（CBD）と進行性核上性麻痺（PSP）は神経病理学的には厳密に鑑別診断は可能だが、臨床的には不能である。現在進行中のCBD/ PSPバイオマーカー蓄積事業は神経病理診断の裏打ちを持たない。
我々の事前検討で、神経病理学的にタウ沈着が両疾患で最も差があるのは、大脳白質と基底核である。本研究は、我々が構築している生前同意ブレインバンク献脳登録者中CBD/ PSPの臨床診断を受けている症例にタウイメージPETを行い大脳白質・基底核の取込みを測定し、死亡時神経病理学的にタウ沈着との関連を得ることで、生前鑑別診断法を確立し、今後の早期診断、早期治療の道につなげる。

Research Products

• [Journal Article] Microglia express gamma-interferon-inducible lysosomal thiol reductase in the brains of Alzheimer's disease and Nasu-Hakola disease. (2018)
  • Author(s): Satoh JI, Kino Y, Yanaizu M, Ishida T, Saito Y
  • Journal Title: Intractable Rare Dis Res. Volume: 7 Pages: 251-257
  • NAID: 130007533903
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive genetic characterizeation of rosette-forming glioneuronal tumors: independent component analysis by tissue microdissection. (2017)
  • Author(s): Kitamura Y, Komori T, Shibuya M, Ohara K, Saito Y, Hayashi S, Sasaki A, Nakagawa E, Tomio R, Kakita A, Nakatsukasa M, Yoshida K, Sasaki H.
  • Journal Title: Brain Pathology Volume: 印刷中 Issue: 1 Pages: 87-93
  • DOI: 10.1111/bpa.12468
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intractable epilepsy due to a rosette-forming glioneuronal tumor with a dysembryoplastic neuroepithelial background. (2017)
  • Author(s): Sumitomo N, Ishiyama A, Shibuya M, Nakagawa E, Kaneko Y, Takahashi A, Otsuki T, Kakita A, Saito Y, Sato N, Sugai K, Sasaki M.
  • Journal Title: Neuropathology Volume: 12 Issue: 3 Pages: 300-304
  • DOI: 10.1111/neup.12450
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transgenic monkey model of the polyglutamine diseases recapitulating progressive neurological symptoms. (2017)
  • Author(s): Tomioka I, Ishibashi H, Minakawa EN, Motohashi HH, Takayama O, Saito Y, Popiel HA, Puentes S, Owari K, Nakatani T, Nogami N, Yamamoto K, Noguchi S, Yonekawa T, Tanaka Y, Fujita N, Suzuki H, Kikuchi H, Aizawa S, Nagano S, Yamada D, Nishino I, Ichinohe N, Wada K, Kohsaka S, Nagai Y, Seki K.
  • Journal Title: eNeuro Volume: 4 Issue: 2 Pages: 0250-56
  • DOI: 10.1523/eneuro.0250-16.2017
  • NAID: 120007100051
  • Peer Reviewed / Open Access
• [Journal Article] Estrogen-Related Factors in the Frontal Lobe of Alzheimer’s Disease Patients and Importance of Body Mass Index (2017)
  • Author(s): Honma Naoko、Saji Shigehira、Mikami Tetuo、Yoshimura Noriko、Mori Seijiro、Saito Yuko、Murayama Shigeo、Harada Nobuhiro
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 726-726
  • DOI: 10.1038/s41598-017-00815-3
  • Peer Reviewed / Open Access
• [Journal Article] Homovanillic acid and 5-hydroxyindole acetic acid as biomarkers for dementia with Lewy bodies and coincident Alzheimer's disease: An autopsy-confirmed study. (2017)
  • Author(s): Morimoto S, Takao M, Hatsuta H, Nishina Y, Komiya T, Sengoku R, Nakano Y, Uchino A, Sumikura H, Saito Y, Kanemaru K, Murayama S.
  • Journal Title: PLoS One Volume: 12 Issue: 2 Pages: e0171524-e0171524
  • DOI: 10.1371/journal.pone.0171524
  • Peer Reviewed / Open Access
• [Journal Article] MR Imaging Features of the Cerebellum in Adult-Onset Neuronal Intranuclear Inclusion Disease: 8 Cases. (2017)
  • Author(s): Sugiyama A, Sato N, Kimura Y, Maekawa T, Enokizono M, Saito Y, Takahashi Y, Matsuda H, Kuwabara S.
  • Journal Title: AJNR Am J Neuroradiol Volume: 38 Issue: 11 Pages: 2100-2104
  • DOI: 10.3174/ajnr.a5336
  • Peer Reviewed / Open Access
• [Presentation] 病理学的見地からみたα-シヌクレインの伝播の病態 (2018)
  • Author(s): 齊藤祐子
  • Organizer: 日本神経学会学術大会
  • Invited
• [Presentation] PDD/DLBの病理 (2018)
  • Author(s): 齊藤祐子
  • Organizer: 第12回パーキンソン病・運動障害疾患コングレス
  • Invited
• [Presentation] 3.Translational from clinic research: from the point of view of neuropathology (2018)
  • Author(s): 齊藤祐子
  • Organizer: 第61回日本神経化学会大会
  • Invited
• [Presentation] To establish all- Japan Brain Bank Network (2018)
  • Author(s): Yuko Saito
  • Organizer: International Congress of Neuropathology
  • Invited
• [Presentation] 認知症画像診断のprogress とpitfall: MRI (2018)
  • Author(s): 齊藤祐子
  • Organizer: 第37回日本認知症学会学術集会
• [Presentation] Establishment of Japan brain bank net; XXIII World Congress of Neurology (2017)
  • Author(s): Saito Y, Kakita A, Yoshida M, Murayama S, Iritani S, Yokota O, Terada S, Ohshima K, Yasuta K, Yabe H, Inoue Y, Tanaka N, Motoyoshi Y, Murata M, Mizusawa,H
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] 国立精神・神経医療研究センターブレインバンク 年次報告 (2017)
  • Author(s): 齊藤祐子, 村山繁雄, 柿田明美, 吉田眞理, 入谷修司, 横田修, 寺田修司, 大島健一, 矢部博興, 國井泰人, 井上悠輔, 田中紀子, 村田美穂, 水澤英洋
  • Organizer: 第58回日本神経病理学会総会学術研究会
  • Int'l Joint Research