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高齢者タウオパチーの臨床分子病理学的研究

Research Project

Project/Area Number 18023041
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
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  東京都老人総合研究所, 研究員 (60344066)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 2007: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2006: ¥3,900,000 (Direct Cost: ¥3,900,000)
Keywords進行性核上性麻痺 / 皮質基底核変性症 / パーキンソン病 / MRI / FDG-PET / ドーパミン / tau / tyrosine hydroxylase / タウ / タウオパチー / 老化 / 進行性核状性麻痺 / 神経原線維変化優位型認知症 / 嗜銀顆粒性認知症 / アルツハイマー病
Research Abstract

PSPのPET所見については,多数の報告がなされているが,その殆どが臨床例で,剖検で確認を得ているものは少ない。また,進行性核上性麻痺(PSP)の形態画像所見としては中脳被蓋の萎縮が古くから指摘されており,臨床的に重要視されている。近年ではMRIの正中矢状断における被蓋/橋面積比を算出する方法が提唱されているが,病理学的裏づけには乏しい。我々はこの両者の所見を剖検例での確認を試みた。
FDG-PETでPSP全例に認める中脳,前帯状回,前頭弁蓋の糖代謝低下は,中脳には対応する4Rタウオパチーが確認できたが,前帯状回・前頭弁蓋ではタウオパチーは軽度であり,タウ蓄積とは異なる病的機序の関与を考えざるを得ない結果であった。
Dopamine-PETの解析で,線条体シナプス前機能と,黒質のTH陽性神経細胞密度の低下が,ともに経過期間に沿って非線形的に減少する傾向を示した。これは呈する症状に関係なく,PSPにおいては黒質、線条体病変が,経時的に進行することを示す所見と考えられた。また,D2受容体密度が比較的保たれ,極早期の一例でむしろ上昇を認めた点は,病理学的にタウオパチーが軽度であることと相関し,臨床的に早期には抗パーキンソン薬が軽度ながら効果を持ち,'パーキンソン病(PD)との鑑別が困難であることの,形態的基盤と考えられた。
中脳被蓋の萎縮はPSP/皮質基底核変性症(CBD)群と正常/PD群との鑑別には有用であるが,PSPとCBDの鑑別には使えないことが明らかとなった。また罹病期間との相関が認められない点は,DA-PET線条体シナプス前機能,黒質TH陽性細胞密度とは異なっており,黒質緻密層以外の要因の関与が,症例間のバリエーションを招いている可能性が示唆された。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (21 results)

All 2007 2006

All Journal Article (14 results) Presentation (5 results) Book (2 results)

  • [Journal Article] Analysis of the adrenal and is usefl for evaluating Pathology of the peripheral autonomic nervous system in Lesy body disease.2007

    • Author(s)
      Fumimura, Y., Ikemura, M., *Salto. Y., Sengoku, R, Kanemaru, K., Sawabe, M., Arai, T., Ito, Cz, 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
  • [Journal Article] Lipocalin-type prostaglandin D synthase/β-trace is a mijor amyloid β-chaperone in humancerebrospinal fluid.2007

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

      PNAS 27

      Pages: 6412-6417

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Neuropathologyofmildcognitiveimpairment2007

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

      Neuropathology 27

      Pages: 578-584

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

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

      J Newol Neurosurg Psychiatry 78

      Pages: 190-192

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

    • Author(s)
      *CairnsN J, Bigio EH, Mackenzie lR, Neumann M, Lee VM, Hatanpaa KJ, Whit.e CL 3rd, Sckmeider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, yokoo H, Mbrayama S, Wbukm J, Mulloz DG Dicksgn DW; Ihce PG, Trojanowski JQ, Man DM
    • Journal Title

      Acta Neuropathol(Berl) 114

      Pages: 5-22

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Prostaglandin D_2 receptor, DPl is selectively up-regulated in microglia and astroes within senile laues from humanpatients and a mouse model of Alzheimer's disease2007

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

      J Neuropath Exp Newol 60

      Pages: 469-480

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Pathology of the sympathetic nervous system corresponding to the decreased cardiac uptake in 123I-metaiodobenzylgunnidine (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: 1151-1158

    • 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, Chida 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, Higio 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, Halliday G, Mackenzie J, Khan N, Ravid R, Dickson D, Wszolek Z, Iwatsubo T, Pickering-Brown SM, Mann DM
    • Journal Title

      Neuropathol Appl Neurobiol 32

      Pages: 374-387

    • Related Report
      2006 Annual Research Report
  • [Presentation] Characterization of therapeutic antibody against Aβ oligomers for Alzheimer's disease2007

    • Author(s)
      Sun, H., Okamoto Y., Kawarabayashi, Kawarabayashi, T., Yokoseki, T., M. Shibata, M., Morishima, , Saito, Y., Muravama.S., Ihaza, Y., Shoji, M., Hoji, M., Michikawa, M., *Matsubara, E
    • Organizer
      2007Society for Neuroscience
    • Place of Presentation
      2007Society for Neuroscience
    • Year and Date
      2007-11-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] TDP43immunocytochemistry is sentisitve but not spec ific method to detect motor neuron-disease type neuronal inclusions2007

    • 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,Japan2007

    • Author(s)
      *Murayama Kanamaru K, Ishii K, Tokumant A
    • Organizer
      2007 World Congress of International Brain Research Organization
    • Place of Presentation
      Melbourne
    • Related Report
      2007 Annual Research Report
  • [Presentation] The Brain Bankfor Aging Research Project,Japan2007

    • 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 nervoussystem in Levwy 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
  • [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: 2006-04-01   Modified: 2018-03-28  

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