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加齢に伴う翻訳後異常修飾蛋白蓄積の相互作用に関する臨床・実験神経病理学的研究

Research Project

Project/Area Number 17390257
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionTokyo Metropolitan Institute of Gerontology

Principal Investigator

村山 繁雄  Tokyo Metropolitan Institute of Gerontology, 東京都老人総合研究所, 研究部長 (50183653)

Co-Investigator(Kenkyū-buntansha) 齊藤 祐子 (斉藤 祐子)  財)東京都高齢者研究・福祉振興財団, 東京都老人総合研究所, 研究員 (60344066)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,080,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2007: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥7,800,000 (Direct Cost: ¥7,800,000)
Keywords老人班 / 神経原線維変化 / 嗜銀顆粒 / レビー小体 / タウ / アルファシヌクレイン / アミロイドベータ蛋白 / ユビキチン / 老人斑 / アミロイドアンギオパチー / αシヌクレイン / アミロイドβ蛋白 / パーキンソン病 / アルツハイマー病 / レヴィー小体 / 老化 / 認知症 / スプライシング
Research Abstract

高齢者の変性型老化性変化の重複沈着の機構を明らかにする目的で、東京都老人医療センター連続開頭剖検例から文書同意を得た、高齢者ブレインバンク(BBAR)登録例に網羅的に、H.E.、KB.染色を通常とし、Gallyas-Braak・Methenamine鍍銀染色に、抗アミロイドβ蛋白(Aβ)(11-24)、リン酸化タウ(AT8)、リン酸化αシヌクレイン(psyn#64)、ユビキチン抗体で免疫染色を行う、BBARプロトコール(www.mci.gr.jp/BrainBank/)に基づき検討した。DNAが保存された1,628例中、老人班(SP)ステージ0-C、神経原線維変化(NFT)ステージI-VIに分類したところ、分散傾向が見られたが、NFT新皮質ステージには、Braak Stage Cが6例の例外を除き要求されることで、アミロイド仮説は新皮質では成立することが明らかとなった。一方、レビー小体型認知症(DLB)コンセンサスガイドライン(1996)に従ったレビースコアと、認知症・パーキンソン症状の有無で分類した、BBARステージ分類I-Vで同一集団を解析したところ、レビースコア新皮質ステージとSPステージCが相関することが明らかとなった。我々が提唱している嗜銀顆粒ステージ分類では、SP、NFTとも相関はみられなかった。一方、末梢自律神経系へのレビー小体病理の進展には、SP Stage C、NFT Stage IV以上が有意の負の相関をとることが明らかとなった。さらに、嗅球のレビー小体病理には、NFT Stageが有意ではないが正の影響を当てることが明らかとなった。以上の点より、新皮質では、タウ、シヌクレインの沈着はAβに影響を受け、辺縁系ではタウとシヌクレインが相互に影響し合い、シヌクレインの末梢への沈着は、アルツハイマー変化が抑制することが明らかとなった。

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (29 results)

All 2007 2006 2005

All Journal Article (21 results) (of which Peer Reviewed: 9 results) Presentation (6 results) Book (2 results)

  • [Journal Article] Analysis of the adrenal gland is useful for evaluating pathology of the peripheral autonomic nervous system in Lesy body disease.2007

    • Author(s)
      Fumimura Y, Ikemura M, Saito Y, Sengoku R, Kanemaru K, Sawabe M, Arai T, Ito G, Iwatsubo T, Fukayama M, Mizusawa H, Muravama S
    • Journal Title

      J Neuropath Exp Neurol 66

      Pages: 469-480

    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Neuropathology of mild cognitive impairment.2007

    • Author(s)
      Saito Y, Murayama S
    • Journal Title

      Neuropathology 104

      Pages: 1387-1393

    • NAID

      10021237082

    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Analysis of the adrenal gland is useful for evaluating pathology of the peripheral autonomic nervous system in Lesy body disease.2007

    • Author(s)
      Fumimura, Y., Ikemura, M., ^*Saitom, Y., Sengoku, R., Kanemaru, K., Sawabe, M., Arai, T., Ito, G., Iwatsubo, T., Fukayama, M., Mizusawa, H., ^*Muravama, S
    • Journal Title

      J Neuropath Exp Neurol 104・5

      Pages: 469-480

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipocalin-type prostaglandin D synthase/β-trace is a major amyloid β-chaperone in human cerebrospinal fluid.2007

    • Author(s)
      Kanekiyo, T., Ban, T., Aritake, K., Huang, Z-L., Qu, W-M., Okazaki, I., Mohri, I., Murayama, S., Ozono, K., Taniike, M., Goto, Y., &^*Urade, Y.
    • Journal Title

      PNAS 27・

      Pages: 6412-6417

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuropathology of mild cognitive impairment.2007

    • Author(s)
      ^*Saito, Y.,& Murayama, S
    • Journal Title

      Neuropathology 27

      Pages: 578-584

    • NAID

      10021237082

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective loss of Purkinje cells in a patient with anti-glutamic acid decarboxylase antibody-associated cerebellar ataxia.2007

    • Author(s)
      ^*Ishida K., Mitoma H., Wada Y., Oka T., Shibahara J. Saito Y., Muravama S., Mizusawa H.
    • Journal Title

      J Neurol Neurosurg Psychiatry 78

      Pages: 190-192

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration:consensus of the Consortium for Frontotemporal Lobar Degeneration.2007

    • Author(s)
      ^*Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL 3rd, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Muravama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, Mann DM
    • Journal Title

      Acta Neuropathol(Berl) 114

      Pages: 5-22

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prostaglandin D_2 receptor, DP_1 is selectively up-regulated in microglia and astrocytes within senile plaques from human patients and a mouse model of Alzheimer's disease.2007

    • Author(s)
      Mohri I, Kadoyama K, Kanekiyo T, Sato Y, Kagitani-Shimono K, Saito Y, Suzuki K, Kudo T, Takeda M, Urade Y, Murayama S, *Taniike M
    • Journal Title

      J Neuropath Exp Neurol 66

      Pages: 469-480

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathology of the sympathetic nervous system corresponding to the decreased cardiac uptake in 123I-metaiodobenzylguanidine (MIBG) scintigraphy in a patient with Parkinson disease.2006

    • Author(s)
      Mitsui J, Saito Y, Momose T, Shimizu J, Arai N, Shibahara J, Ugawa Y, Kanazawa I, Tsuji S, Murayama S
    • Journal Title

      J Neurol Sci 243

      Pages: 101-104

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Multiple candidate gene analysis identifies a-synuclein as a susceptibility gene for sporadic Parkinson's disease.2006

    • Author(s)
      Mizuta I, Satake W, Nakabayashi Y, Ito C, Suzuki S, Momose Y, Nagai Y, Oka A, Inoko H, Fukae J, Saito Y, Sawabe M, Murayama S, Yamamoto M, Hattori N, Murata M, Toda T
    • Journal Title

      Hum Mol Gen 15

      Pages: 1151-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Beta-site APP cleaving enzyme 1 (BACE1) is increased in remaining neurons in Alzheimer's disease brains.2006

    • Author(s)
      Harada H, Tamaoka A, Ishii K, Shoji S, Kametaka S, Kametani F, Saito Y, Murayama S:
    • Journal Title

      Neurosci Res 54

      Pages: 24-29

    • NAID

      10020614044

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increased levels of granular tau oligomers : an early sign of brain aging and Alzheimer's disease.2006

    • Author(s)
      Maeda S, Sahara N, Saito Y, Murayama S, Ikai A, Takashima A
    • Journal Title

      Neurosci Res 54

      Pages: 179-201

    • NAID

      10017323753

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Autotaxin expression is enhanced in frontal cortex of Alzheimer-type dementia patients.2006

    • Author(s)
      Umemura K, Yamashita N, Yu X, Arima K, Asada T, Makifuchi T, Murayama S, Saito Y, Kanamaru K, Goto Y, Kohsaka S, Kanazawa I, Kimura H
    • Journal Title

      Neurosci Lett 400

      Pages: 97-100

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Sustained progression and loss of the gender-related difference in atherosclerosis in the very old : A pathological study of 1074 consecutive autopsy cases.2006

    • Author(s)
      Sawabe M, Arai T, Kasahara I, Hamamatsu A, Esaki Y, Nakahara K, Harada K, Chiba K, Yamanouchi H, Ozawa T, Takubo K, Murayama S, Tanaka N
    • Journal Title

      Atherosclerosis 186

      Pages: 374-379

    • Related Report
      2006 Annual Research Report
  • [Journal Article] An immunohistochemical study of cases of sporadic and inherited forntotemproal lobar degeneration using 3R-and 4R-spefici tau monoclonal antibodies.2006

    • Author(s)
      Silva R, Lashely T, Strand C, Shiarli AM, Shi J, Tian J, Bailery, KL, Davies P, Higo EH, Arima K, Iseki E, Murayama S, Kretzschmar H, Neumann M, Lippa C, Halliday G, Mackenzie J, Ravid R, Dicskon D, Wszolek Z, Iwatsubo T, Pickering-Brosn SM, Hoton J, Lees A, Tavesz T, Mann DMA
    • Journal Title

      Acat Neuropathologica 111

      Pages: 329-340

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease.2006

    • Author(s)
      Shiarli AM, Jennings R, Shi J, Bailey K, Davidson Y, Tian J, Bigio EH, Ghetti B, Murrell JR, Delisle MB, Mirra S, Crain B, Zolo P, Arima K, Iseki E, Murayama S, Kretzschmar H, Neumann M, Lippa C, Haliday G, Mackenzie J, Khan N, Ravid R, Dickson D, Wazolek Z, Iwatsubo T, Pickering-Brown SM, Mann DM
    • Journal Title

      Neuropathol Appl Neurobiol 32

      Pages: 374-387

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Unique tauopathy in Fukuyama-type congenital muscular dystrophy.2005

    • Author(s)
      Saito Y, Motoyoshi Y, Kashima T, Izumiyama-Shimomura N, Toda T, Nakano I, Hasegawa M, Murayama S
    • Journal Title

      J Neuropath Exp Neurol 64

      Pages: 1118-1126

    • Related Report
      2007 Final Research Report Summary 2005 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Idependent accumulations of tau and amyloid β-protein in the human entorhinal cortex.2005

    • Author(s)
      Katsuno T, Morishima-Kawashima M, Saito Y, Yamanouchi H, Ishiura S, Murayama S, Ihara Y
    • Journal Title

      Neurology 64

      Pages: 687-692

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's disease.2005

    • Author(s)
      Ishigami A, Ohsawa T, Hiratsuka M, Taguchi H, Kobayashi S, Saito Y, Murayama S, Asaga H, Toda T, Kimura N, Maruyama N
    • Journal Title

      Neurosci Res 80

      Pages: 120-128

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Possibility for neurogenesis in the substantia nigra of Parkinsonian brain.2005

    • Author(s)
      Yoshimi K, Ren Yong-Ri, Seki T, Yamada M, Ooizumi H, Onodera M, Saito Y, Murayama S, Okano H, Mizuno Y, Mochizuki H
    • Journal Title

      Ann Neurol 58

      Pages: 31-40

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Possibility for neurogenesis in the substantia nigra of Parkinsonian brain.2005

    • Author(s)
      Saito Y, Motoyoshi Y, Kashima T, Izumiyama-Shimomura N, Toda T, Nakano I, Hasegawa M, Murayama S
    • Journal Title

      Ann Neurol 58

      Pages: 31-40

    • Related Report
      2005 Annual Research Report
  • [Presentation] Characterization of therapeutic antibody against Aβ oligomcrs for Alzheimer's disease.2007

    • Author(s)
      Sun, H., Okamoto Y., Kawarabayashi, Kawarabayashi, T., Yokoseki, T., M. Shibata, M., Morishima,, Saito, Y., Murayama, S., Ihara, Y., Shoji, M., Hoji, M., Michikawa, M., *Matsubara, E
    • Organizer
      2007Society for Neuroscience
    • Place of Presentation
      San Diego
    • Year and Date
      2007-11-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] TDP 43 immunocytochemistry is sentisitve but not specific method to detect motor neuron-disease type neuronal inclusions.2007

    • Author(s)
      *Murayama S, Saito Y, Hatsuta H:
    • Organizer
      83rd Annual Meeting of the Amerian Association for Neuropathologists
    • Place of Presentation
      Wahington D.C.
    • Related Report
      2007 Annual Research Report
  • [Presentation] The Brain Bank for Aging Research,Japan.2007

    • Author(s)
      *Murayama S, Saito Y, Kanamaru K, Ishii K, Tokumaru A
    • Organizer
      2007World Congress of International Brain Research Organization
    • Place of Presentation
      Melbourne
    • Related Report
      2007 Annual Research Report
  • [Presentation] The Brain Bank for Aging Research Project, Japan.2007

    • Author(s)
      *Murayama S, Saito Y, Kanamaru K, Ishii K, Tokumaru A
    • Organizer
      Intenational Geriatric Psychiatry
    • Place of Presentation
      Osaka
    • Related Report
      2007 Annual Research Report
  • [Presentation] Adrenal gland is useful to evaluate peripheral autonomic nervous system in Lewy body disease.2007

    • Author(s)
      *Murayama S, Saito Y, Ikemura M
    • Organizer
      5th Congress of the International Society for Autonomic Neuroscience
    • Place of Presentation
      Kyoto
    • Related Report
      2007 Annual Research Report
  • [Presentation] Synergetic effect of Alzheimer and Parkinson changes on dementia.2005

    • Author(s)
      Saito Y, Kanemaru K, Arai T, Sawabe M, Murayama S
    • Organizer
      World Congress of Neurology
    • Place of Presentation
      Sydney
    • Related Report
      2007 Final Research Report Summary
  • [Book] Annual Review神経病理2007、中外医学社、東京2007

    • Author(s)
      村山 繁雄, 齊藤 祐子
    • Publisher
      PDD(認知症を伴うパーキンソン病)とDLB(レヴィー小体型認知症)の臨床と病理。
    • Related Report
      2007 Annual Research Report
  • [Book] アルツハイマー病診断2006

    • Author(s)
      村山繁雄 編著
    • Total Pages
      234
    • Publisher
      真興交易 (株)医書出版部
    • Related Report
      2006 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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