Neuropathologic analysis of small vessel diseases of the cerebral white matter in association with sporadic and hereditary dementia

• Project/Area Number: 23500435
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: TAKAO MASAKI 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (50245487)
• Co-Investigator(Kenkyū-buntansha): SAITO Yuko 独立行政法人国立精神・神経医療研究センター, 臨床検査部, 室長 (60344066)
• Research Collaborator: ITO S 虎ノ門病院, 病理, 医師
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 脳・神経 / 病理学 / 脳血管疾患 / 認知症 / 神経科学 / 長寿命化 / 生体材料

Research Abstract

The aim of the present study is to clarify the role of small vessel diseases in the cerebral white matter in dementia individuals. We carried out clinical and neuropathologic studies of 1) CARASIL cases, 2) mildly demented (CDR=0.5) individuals and 3) morphological analysis of small vessels in the cerebral white matter and putamen. The small vessels of CARASIL showed multilayers of elastic membranes and thinning of tunica media. Those findings were different from those of usual atherosclerotic changes. Frequency of cerebrovascular diseases was relatively high in mildly demented cases. However, the rate of cerebrovascular diseases decreased with increase of age. The lumen of small vessels in the cerebral white matter decreased with increasing grade of Braak stages of neurofibrillary tangles. Our multidisciplinary approaches suggest that small vessel diseases are important to understand dementia cases.

Research Products

• [Journal Article] Imaging spectrum of sporadic cerebral amyloid angiopathy : multifaceted features of a single pathological condition (2014)
  • Author(s): Sakurai K, Tokumaru AM, Nakatsuka T, Murayama S, Hasebe S, Imabayashi E, Kanemaru K, Takao M, Hatsuta H, Ishii K, Saito Y, Shibamoto Y, Matsukawa N, Chikui E, Terada H
  • Journal Title: Insights Imaging Volume: (in press)
  • URL: http://link.springer.com/article/10.1007/s13244-014-0312-x
  • Peer Reviewed
• [Journal Article] 血管性認知症の臨床とその背景, 問題点 (2014)
  • Author(s): 高尾昌樹
  • Journal Title: 血管医学 Volume: 15 Pages: 1-8
• [Journal Article] The Feasibility of White Matter Volume Reduction Analysis using SPM8 plus DARTEL for the Diagnosis of Patients with Clinically Diagnosed Corticobasal Syndrome and Richardson's Syndrome (2014)
  • Author(s): Sakurai K, Imabayashi E, Tokumaru A, Hasebe S, Murayama S, Morimoto S, Kanemaru K, Takao M, Shibamoto Y, Matsukawa N
  • Journal Title: Neuroimage clinical Volume: (in press) Pages: 605-610
  • DOI: 10.1016/j.nicl.2014.02.009
  • Peer Reviewed
• [Journal Article] Imaging spectrum of sporadic cerebral amyloid angiopathy: multifaceted features of a single pathological condition (2014)
  • Author(s): Sakurai K, Tokumaru AM, Nakatsuka T, Murayama S, Hasebe S, Imabayashi E, Kanemaru K, Takao M, Hatsuta H, Ishii K, Saito Y, Shibamoto Y, Matsukawa N, Chikui E, Terada H.
  • Journal Title: Insights Imaging Volume: Feb
  • Peer Reviewed
• [Journal Article] 血管性認知症の臨床とその背景，問題点 (2014)
  • Author(s): 髙尾昌樹
  • Journal Title: 血管医学 Volume: 15 Pages: 1-8
• [Journal Article] 軽度認知障害の神経病理 (2013)
  • Author(s): 高尾昌樹
  • Journal Title: 神経内科 Volume: 78 Pages: 703-715
• [Journal Article] 神経病理基盤に関する今日的理解 (2013)
  • Author(s): 高尾昌樹
  • Journal Title: 高次脳機能研究 Volume: 33 Pages: 310-317
• [Journal Article] Increased number of astrocytes and macrophages/microglial cells in the corpus callosum in amyotrophic lateral sclerosis (2013)
  • Author(s): Sugiyama M, Takao M, Hatsuta H, Funabe S, Ito S, Obi T, Tanaka F, Kuroiwa Y, Murayama S.
  • Journal Title: Neuropathology Volume: 34 Issue: 6 Pages: 591-9
  • DOI: 10.1111/neup.12027
  • Peer Reviewed
• [Journal Article] Neuropathologic analysis of Lewy- related alpha- synucleinopathy in olfactory mucosa. (2013)
  • Author(s): Funabe S
  • Journal Title: Neuropathology Volume: 33 Issue: 1 Pages: 47-58
  • DOI: 10.1111/j.1440-1789.2012.01329.x
  • Peer Reviewed
• [Journal Article] ラクナ梗塞の病理と発症機序 (2013)
  • Author(s): 高尾昌樹
  • Journal Title: 神経内科 Volume: 74 Pages: 217-226
• [Journal Article] Molecular analysis and biochemical classification of TDP-43 proteinopathy (2012)
  • Author(s): Tsuji H
  • Journal Title: Brain Volume: 135(11) Issue: 11 Pages: 3380-91
  • DOI: 10.1093/brain/aws230
  • Peer Reviewed
• [Journal Article] Neuropathology of mild cognitive impairment (2012)
  • Author(s): Takao M
  • Journal Title: Rinsho Shinkeigaku Volume: 52 Pages: 851-854
  • NAID: 130004505183
• [Journal Article] Reduced brain-derived neurotrophic factor (BDNF) mRNA expression and presence of BDNF-immunoreactive granules in the spinocerebellar ataxia type 6 (SCA6) cerebellum (2012)
  • Author(s): Takahashi M, Ishikawa K, Sato N, Obayashi M, Niimi Y, Ishiguro T, Yamada M, Toyoshima Y, Takahashi H, Kato T, Takao M, Murayama M, Mori O, Eishi Y, Mizusawa H
  • Journal Title: Neuropathology Volume: (in press) Issue: 6 Pages: 593-603
  • DOI: 10.1111/j.1440-1789.2012.01302.x
  • Peer Reviewed
• [Journal Article] Superficial siderosis associated with abundant tau and α-synuclein accumulation (2011)
  • Author(s): Takao M, Murayama S, Yoshida Y, Mihara B
  • Journal Title: BMJ Case Reports published online 1 December Volume: December Pages: 1-7
  • DOI: 10.1136/bcr.10.2011.4925
  • Peer Reviewed
• [Presentation] 皮質下梗塞と白質脳症を伴う常染色体劣性脳動脈症(CARASIL)遺伝子診断された3剖検例を用いた病理学的検討 (2013)
  • Author(s): 伊藤慎治, 高尾昌樹, 仁木利郎, 伊藤信夫, 福武敏夫, 下江豊, 深山正久, 村山繁雄
  • Organizer: 第102回日本病理学会総会
• [Presentation] ブレインバンク研究班 ブレインバンク(BB)に関する調査研究(文科省脳科学研究戦略推進プログラム脳基盤研究)の結果概要報告 (2013)
  • Author(s): 有馬邦正, 武田伸一, 丸山英二, 松下一章, 木原章子, 服部功太郎, 柿田明美, 豊島靖子, 村山繁雄, 高尾昌樹, 富田博秋, 手嶋豊, 磯部哲, 佐藤雄一郎, 伏木信次, 辻村貴子, 佐藤啓造, 丹羽真一, 武藤香織, 井上悠輔, 辰井聡子, 伊藤雅之, 黒木規臣, 石川 正憲, 齊藤祐子, Lin Crystal
  • Organizer: 第54回日本神経病理学会総会学術研究会
• [Presentation] 皮質下梗塞と白質脳症を伴う常染色体劣性脳動脈症（CARASIL）遺伝子診断された３剖検例を用いた病理学的検討 (2013)
  • Author(s): 伊藤慎治，高尾昌樹，仁木利郎，伊藤信夫，福武敏夫，下江豊，深山正久，村山繁雄
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: 札幌
• [Presentation] ブレインバンク研究班 ブレインバンク（BB）に関する調査研究（文科省脳科学研究戦略推進プログラム脳基盤研究）の結果概要報告 (2013)
  • Author(s): 有馬邦正, 武田伸一, 丸山英二, 松下一章, 木原章子, 服部功太郎, 柿田明美, 豊島靖子, 村山繁雄, 高尾昌樹, 富田博秋, 手嶋豊, 磯部哲, 佐藤雄一郎, 伏木信次, 辻村貴子, 佐藤啓造, 丹羽真一, 武藤香織, 井上悠輔, 辰井聡子, 伊藤雅之, 黒木規臣, 石川 正憲, 齊藤祐子, Lin Crystal
  • Organizer: 第54回日本神経病理学会総会学術研究会
  • Place of Presentation: 東京
• [Presentation] 軽度認知障害の背景にある神経病理所見とは (2012)
  • Author(s): 高尾昌樹
  • Organizer: 第3回日本血管性認知障害研究会
  • Year and Date: 2012-09-08
  • Invited
• [Presentation] 軽度認知障害の神経病理 (2012)
  • Author(s): 高尾昌樹
  • Organizer: 第53回日本神経学会総会
• [Presentation] シンポジムII 「進行性失語」 神経病理基盤に関する今日的理解 (2012)
  • Author(s): 高尾昌樹
  • Organizer: 第36回日本高次機能障害学会学術総会
• [Presentation] New Observations in Gerstmann-Straussler-Scheinker Disease Associated with the PRNP A117V Mutation (2012)
  • Author(s): Takao M, Spina S, Murrell J, Epperson F, Glazier B, Farlow M, Unverzagt F, Saykin S, Yoder K, Risacher S, Kepe V, Barrio J
  • Organizer: The 88th Annual meeting of the American Association of Neuropathologists, Inc
• [Presentation] Clinical and Neuropathologic Heterogeneity in PSEN1 A431E (2012)
  • Author(s): Murrell J, Mehta R, Bigio E, Cairns N, Cochran E, Gitelman D, Head E, Leverenz J, Poon W, Takao M, Weintraub S, Ringman J, Ghetti B
  • Organizer: The 88th Annual meeting of the American Association of Neuropathologists, Inc
• [Presentation] シンポジムII 「進行性失語」 神経病理基盤に関する今日的理解 (2012)
  • Author(s): 高尾昌樹
  • Organizer: 第36回日本高次機能障害学会学術総会
  • Place of Presentation: 宇都宮
  • Invited
• [Presentation] New Observations in Gerstmann-Stra¨ussler-Scheinker Disease Associated with the PRNP A117V Mutation (2012)
  • Author(s): Takao M, Spina S, Murrell J, Epperson F, Glazier B, Farlow M, Unverzagt F, Saykin S, Yoder K, Risacher S, Kepe V, Barrio J.
  • Organizer: The 88th Annual meeting of the American Association of Neuropathologists, Inc.
  • Place of Presentation: シカゴ
• [Presentation] Clinical and Neuropathologic Heterogeneity in PSEN1 A431E (2012)
  • Author(s): Murrell J, Mehta R, Bigio E, Cairns N, Cochran E, Gitelman D, Head E, Leverenz J, Poon W, Takao M, Weintraub S, Ringman J, Ghetti B.
  • Organizer: The 88th Annual meeting of the American Association of Neuropathologists, Inc.
  • Place of Presentation: シカゴ
• [Presentation] 皮質下梗塞と白質脳症を伴う常染色体劣性脳動脈症(CARASIL)の54歳男性剖検例 (2011)
  • Author(s): 伊藤慎治、高尾昌樹、野上茜、舟辺さやか、初田裕幸、赤津裕康、下江豊、福武敏夫、村山繁雄
  • Organizer: 第98回 日本神経病理学会関東地方会
  • Place of Presentation: 東京医科歯科大学
• [Presentation] 皮質下梗塞と白質脳症を伴う常染色体劣性脳動脈症(CARASIL)の54 歳男性剖検例
  • Author(s): 伊藤慎治, 高尾昌樹, 野上茜, 舟辺さやか, 初田 裕幸, 赤津裕康, 下江豊, 福武敏夫, 村山繁雄
  • Organizer: 第98回日本神経病理学会関東地方会
• [Book] その他各種検査．中島健二，天野直二，下濱俊，冨本秀和，三村 將 編．認知症ハンドブック (2013)
  • Author(s): 髙尾昌樹
  • Publisher: 医学書院
• [Book] 脳血管性認知症 田中耕太郎、高島修太郎 編．必携脳卒中ハンドブック 改訂第2版 (2011)
  • Author(s): 高尾昌樹
  • Publisher: 診断と治療社
• [Book] 脳血管性認知症 田中耕太郎, 高島修太郎 編.必携脳卒中ハンドブック 改訂第2版
  • Author(s): 高尾昌樹
  • Publisher: 診断と治療社