Analysis of pathophysiology of hereditary cerebral amyloid angiopathy associated with amyloidgenic transthyretin Y114C

2013 Fiscal Year Final Research Report

• Project/Area Number: 23500430
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Kumamoto University
• Principal Investigator: YAMASHITA Taro 熊本大学, 生命科学研究部, 講師 (90381003)
• Co-Investigator(Kenkyū-buntansha): ANDO Yukio 熊本大学, 生命科学研究部・神経内科学分野, 教授 (20253742) ; HIRAHARA Tomoo 熊本大学, 医学部附属病院・神経内科, 助教 (80649343)
• Project Period (FY): 2011 – 2013
• Keywords: 脳アミロド血管症 / トランスサイレチン / 認知症 / 脳出血 / 脳血管透過性亢進 / 肝移植 / 治療

Research Abstract

Patients with amyloidogenic transthyretin (TTR) Y114C develop amyloid deposits in cerebral blood vessels, cerebral hemorrhage, and rapidly progressive dementia that presents with hereditary cerebral amyloid angiopathy (CAA). MRI studies with FLAIR images after Gd administration showed Gd leakage into the subarachnoid space. The pathogenesis of CNS disorders may reflect disruption of the blood-CSF barrier and blood-brain barrier by amyloid deposition. The mortality and occurrence of cerebral hemorrhage and dementia in patients having transplantations were reduced compared with those in patients not having transplantations. The group undergoing transplantations had significantly smaller volumes of intracranial hemorrhage than did the no-transplantation group. Liver transplantation was effective for CNS manifestations of cerebral amyloid angiopathy associated with amyloidogenic transthyretin Y114C.

Research Products

• [Journal Article] Gait disturbance due to foot drop is refractory to treatment in nonsystemic vasculitic neuropathy (2014)
  • Author(s): Hirahara T, Yamashita S, Misumi Y, Kawakami K, Hori H, Honda S, Watanabe M, Ikeda T, Yamashita T, Maeda Y, Ando Y
  • Journal Title: Eur Neurol Volume: 71(3-4) Pages: 180-6
  • DOI: 10.1159/000355531
  • Peer Reviewed
• [Journal Article] Diflunisal Trial Consortium. Repurposing diflunisal for familial amyloid polyneuropathy : a randomized clinical trial (2013)
  • Author(s): Berk JL, Suhr OB, Obici L, Sekijima Y, Zeldenrust SR, Yamashita T, Heneghan MA, Gorevic PD, Litchy WJ, Wiesman JF, Nordh E, Corato M, Lozza A, Cortese A, Robinson-Papp J, Colton T, Rybin DV, Bisbee AB, Ando Y, Ikeda S, Seldin DC, Merlini G, Skinner M, Kelly JW, Dyck PJ
  • Journal Title: JAMA Volume: 310(24) Pages: 2658-67
  • DOI: 10.1001/jama.2013.283815
  • Peer Reviewed
• [Journal Article] Effect of age and sex differences on wild-type transthyretin amyloid formation in familial amyloidotic polyneuropathy : a proteomic approach (2013)
  • Author(s): Tasaki M, Ueda M, Obayashi K, Koike H, Kitagawa K, Ogi Y, Jono H, Su Y, Suenaga G, Oshima T, Misumi Y, Yoshida M, Yamashita T, Sobue G, Ando Y
  • Journal Title: Int J Cardiol Volume: 170(1) Pages: 69-74
  • DOI: 10.1016/j.ijcard.2013.10.033
  • Peer Reviewed
• [Journal Article] Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10 years after liver transplantation (2013)
  • Author(s): Oshima T, Kawahara S, Ueda M, Kawakami Y, Tanaka R, Okazaki T, Misumi Y, Obayashi K, Yamashita T, Ohya Y, Ihse E, Shinriki S, Tasaki M, Jono H, Asonuma K, Inomata Y, Westermark P, Ando Y
  • Journal Title: J Neurol Neurosurg Psychiatry
  • DOI: 10.1136/jnnp-2013-305973
  • Peer Reviewed
• [Journal Article] Dominant cardiac type of familial amyloidotic polyneuropathy associated with a novel transthyretin variant Thr59Arg (2013)
  • Author(s): Obayashi K, Misumi Y, Watanabe T, Ando T, Akagami T, Tasaki M, Shinriki S, Ueda M, Yamashita T, Hirotani S, Ando Y
  • Journal Title: Muscle Nerve Volume: 48(5) Pages: 839-41
  • DOI: 10.1002/mus.23939
  • Peer Reviewed
• [Journal Article] Marked cardiomegaly in a patient with familial amyloidotic polyneuropathy after orthotopic liver transplantation : a case study (2013)
  • Author(s): Sakashita N, Kagawa S, Date R, Ueno T, Nakagawa T, Yamashita T, Obayashi K, Ohshima T, Ueda M, Horiguchi H, Ando Y, Takeya M
  • Journal Title: Pathol Int Volume: 63(5) Pages: 260-5
  • DOI: 10.1111/pin.12055
  • Peer Reviewed
• [Journal Article] Amyloid fibrils containing fragmented ATTR may be the standard fibril composition in ATTR amyloidosis (2013)
  • Author(s): Ihse E, Rapezzi C, Merlini G, Benson MD, Ando Y, Suhr OB, Ikeda S, Lavatelli F, Obici L, Quarta CC, Leone O, Jono H, Ueda M, Lorenzini M, Liepnieks J, Ohshima T, Tasaki M, Yamashita T, Westermark P
  • Journal Title: Amyloid Volume: 20(3) Pages: 142-50
  • DOI: 10.3109/13506129.2013.797890
  • Peer Reviewed
• [Journal Article] Impact of antibodies against amyloidogenic transthyretin (ATTR) on phenotypes of patients with familial amyloidotic polyneuropathy (FAP) ATTR Valine30Methionine (2013)
  • Author(s): Obayashi K, Tasaki M, Jono H, Ueda M, Shinriki S, Misumi Y, Yamashita T, Oshima T, Nakamura T, Ikemizu S, Anan I, Suhr O, Ando Y
  • Journal Title: Clin Chim Acta Volume: 419 Pages: 127-31
  • DOI: 10.1016/j.cca.2013.02.002
  • Peer Reviewed
• [Journal Article] Bilateral basal ganglia lesions as initial manifestation of CNS invasion in adult T-cell leukemia (2013)
  • Author(s): Matsuo Y, Yamashita S, Honda S, Nakajima M, Ueda A, Hirahara T, Yamashita T, Maeda Y, Hirano T, Ando Y
  • Journal Title: J Neurol Sci Volume: 327(1-2) Pages: 63-4
  • DOI: 10.1016/j.jns.2013.01.035
  • Peer Reviewed
• [Journal Article] Muscle biopsy findings predictive of malignancy in rare infiltrative dermatomyositis (2013)
  • Author(s): Uchino M, Yamashita S, Uchino K, Mori A, Hara A, Suga T, Hirahara T, Koide T, Kimura E, Yamashita T, Ueda A, Kurisaki R, Suzuki J, Honda S, Maeda Y, Hirano T, Ando Y
  • Journal Title: Clin Neurol Neurosurg Volume: 115(5) Pages: 603-6
  • DOI: 10.1016/j.clineuro.2012.07.019
  • Peer Reviewed
• [Journal Article] Long-term survival after liver transplantation in patients with familial amyloid polyneuropathy (2012)
  • Author(s): Yamashita T, Ando Y, Okamoto S, Misumi Y, Hirahara T, Ueda M, Obayashi K, Nakamura M, Jono H, Shono M, Asonuma K, Inomata Y, Uchino M
  • Journal Title: Neurology Volume: 78(9) Pages: 637-43
  • DOI: 10.1212/WNL.0b013e318248df18
  • Peer Reviewed
• [Journal Article] Pathological changes long after liver transplantation in a familial amyloidotic polyneuropathy patient (2012)
  • Author(s): Obayashi K, Ueda M, Oshima T, Kawahara S, Misumi Y, Yamashita T, Jono H, Yazaki M, Kametani F, Ikeda S, Ohya Y, Asonuma K, Inomata Y, Ando Y
  • Journal Title: BMJ Case Rep Pages: bcr2012006593
  • DOI: 10.1136/bcr-2012-006593
  • Peer Reviewed
• [Journal Article] Relationship between amyloid deposition and intracellular structural changes in familial amyloidotic polyneuropathy (2012)
  • Author(s): Misumi Y, Ueda M, Obayashi K, Jono H, Su Y, Yamashita T, Ohshima T, Ando Y, Uchino M
  • Journal Title: Hum Pathol Volume: 43(1) Pages: 96-104
  • DOI: 10.1016/j.humpath.2011.01.036
  • Peer Reviewed
• [Journal Article] Effect of liver transplantation on the survival of patients with ordinary onset familial amyloid polyneuropathy in Japan (2011)
  • Author(s): Yamashita T, Ando Y, Okamoto S, Yohei M, Hitahara T, Ueda M, Obayashi K, Nakamura M, Jono H, Asonuma K, Inomata Y, Uchino M
  • Journal Title: Amyloid Volume: Suppl1 Pages: 185-6
  • DOI: 10.3109/13506129.2011.574354069
  • Peer Reviewed
• [Journal Article] Spinal multifocal amyloidosis derived from wild-type transthyretin (2011)
  • Author(s): Sueyoshi T, Ueda M, Sei A, Misumi Y, Oshima T, Yamashita T, Obayashi K, Shinriki S, Jono H, Shono M, Ando Y, Mizuta H
  • Journal Title: Amyloid Volume: 8(3) Pages: 165-8
  • DOI: 10.3109/13506129.2011.582197
  • Peer Reviewed
• [Journal Article] Amyloid neuropathy in a younger domino liver transplanted recipient (2011)
  • Author(s): Obayashi K, Yamashita T, Tasaki M, Ueda M, Shono M, Jono H, Ohshima T, Ohya Y, Asonuma K, Inomata Y, Ando Y
  • Journal Title: Muscle Nerve Volume: 3(3) Pages: 449-50
  • DOI: 10.1002/mus.21941
  • Peer Reviewed
• [Presentation] Transthyretin Y114C-related Angitis in Cerebral Amyloid Angiopathy after Liver Transplantation (2013)
  • Author(s): Yamashita T, Ohnishi K, Okumura K, Oshima T, Inoue Y, Misumi Y, Suga T, Ueda A, Ueda M, Yamashita S, Maeda Y, Shinriki S, Obayashi K, Sakashita N, Takeya M, Ando Y
  • Organizer: IXth International Symposium on Familial Amyloidotic Polyneuropathy (ISFAP) and the VIIIth International Symposium on Liver Transplantation in Familial Amyloidotic Polyneuropathy
  • Place of Presentation: Rio de Janeiro, Brazil
  • Year and Date: 20131110-13
• [Presentation] ATTR Y114C 型脳アミロイド血管症剖検例における神経病理学的検討 (2013)
  • Author(s): 山下太郎, 大嶋俊範, 田崎雅義, 道鬼つかさ, 三隅洋平, 神力悟, 植田光晴, 城野博史, 大林光念, 山下賢, 前田寧, 安東由喜雄
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 20130529-0606
• [Presentation] An Autopsy Case of Transthyretin Y114C-related Cerebral Amyloid Angiopathy after Liver Transplantation (2013)
  • Author(s): Yamashita T, Koji Onishi, Kosuke Okumura, Toshinori Oshima, Yasuteru Inoue, Yohei Misumi, Tomohiro Suga, Akihiko Ueda, Mitsuharu Ueda, Satoshi Yamashita, Yasushi Maeda, Satoru Shinriki, Konen Obayashi, Naomi Sakashita, Motohiro Takeya, Ando Y
  • Organizer: American Academy of Neurology 65th Annual Meeting
  • Place of Presentation: San Diego
  • Year and Date: 20130316-23
• [Presentation] FAP 患者肝を用いたドミノ移植患者剖検例におけるアミロイド沈着様式の検討 (2013)
  • Author(s): 山下太郎, 小池春樹, 大嶋俊範, 磯野香織, 田崎雅義, 三隅洋平, 植田光晴, 神力悟, 大林光念, 城野博史, 祖父江元, 安東由喜雄
  • Organizer: 平成24年度アミロイドーシスに関する調査研究班研究報告会
  • Place of Presentation: 東京
  • Year and Date: 20130124-25
• [Presentation] サイバニクスによる家族性アミロイドポリニューロパチー(FAP) 患者における運動障害改善効果の検討 (2013)
  • Author(s): 山下太郎, 中西俊人, 道鬼つかさ, 井上泰輝, 三隅洋平, 植田明彦, 植田光晴, 平原智雄, 渡邊聖樹, 山下賢, 前田寧, 大林光念, 安東由喜雄
  • Organizer: 第1回日本アミロイドーシス研究会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2013-08-30
• [Presentation] トランスサイレチンY114C 型遺伝性脳アミロイド血管症患者における肝移植後の臨床症候の長期的変化 (2012)
  • Author(s): 奥村幸祐, 山下太郎, 立石真知子, 大嶋俊範, 植田明彦, 三隅洋平, 平原智雄, 本田省ニ, 植田光晴, 大林光念, 山下 賢, 前田 寧, 安東由喜雄
  • Organizer: 第30回日本神経治療学会総会
  • Place of Presentation: 北九州
  • Year and Date: 20121128-30
• [Presentation] Early TTR-FAP patient identification and diagnosis - the example of Japan (2012)
  • Author(s): Yamashita T, Ando Y
  • Organizer: TTR-FAP Global Commercial Advisory Board
  • Place of Presentation: London, UK
  • Year and Date: 20121018-19
• [Presentation] 家族性アミロイドポリニューロパチーにおける臨床症候に対する肝移植の長期的効果の検討 (2012)
  • Author(s): 山下太郎, 奥村幸祐, 大嶋俊範, 三隅洋平, 植田明彦, 菅 智宏, 神力 悟, 植田光晴, 城野博史, 大林光念, 山下 賢, 前田 寧, 安東由喜雄
  • Organizer: 第23回日本末梢神経学会学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 20120831-0901
• [Presentation] ATTR Y114C 型脳アミロイド血管症におけるアミロイド沈着の分布の解析 (2012)
  • Author(s): 山下太郎, 大嶋俊範, 奥村幸祐, 永利聡仁, 立石真知子, 三隅洋平, 神力 悟, 植田光晴, 大林光念, 城野博史, 安東由喜雄
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 20120522-25
• [Presentation] Detection of Microbleeds in Hereditary Cerebral Amyloid Angiopathy Associated with Amyloidgenic Transthyretin Tyr114Cys Using Susceptibility-weighted Imaging (2012)
  • Author(s): Yamashita T, Hirano T, Hirai T, Oshima T, Okumura K, Tateishi M, Yohei M, Yamashita S, Maeda Y, Shinriki S, Ueda M, Obayashi K, Ando Y
  • Organizer: XIII International Symposium on Amyloidosis
  • Place of Presentation: Groningen, The Netherlands
  • Year and Date: 20120506-10
• [Presentation] Effect of Liver Transplantation on Peripheral Neuropathy of Familial Amyloid Polyneuropathy V30M (2011)
  • Author(s): Yamashita T, Oshima T, Okumur K, Nagatoshi A, Misumi M, Okamoto S, Ueda A, Ueda M, Obayashi K, Nakamura M, Jono H, Shono M, Asonuma K, Ando Y, Inomata Y
  • Organizer: VIIIth International Symposium on Familial Amyloidotic Polyneuropathy and VIIth International Symposium on Liver Transplantation in Familial Amyloidotic Polyneuropathy
  • Place of Presentation: Kumamoto
  • Year and Date: 20111120-22
• [Presentation] A Case of Familial Amyloidotic Polyneuropathy ATTR Ser77Tyr : The First Report from Japan (2011)
  • Author(s): Nagatoshi A, Yamashita T, Nagano H, Teramoto S, Okumura K, Oshima K, Misumi Y, Okamoto S, Ueda A, Ueda M, Obayashi K, Jono 2, Shono M, Ando Y
  • Organizer: VIIIth International Symposium on Familial Amyloidotic Polyneuropathy and VIIth International Symposium on Liver Transplantation in Familial Amyloidotic Polyneuropathy
  • Place of Presentation: Kumamoto
  • Year and Date: 20111120-22
• [Presentation] Long-term Outcome of Clinical Manifestations after Liver Transplantation in Patients with Familial Amyloid Polyneuropathy Val30Met (2011)
  • Author(s): Okumura K, Yamashita T, Oshima T, Nagatoshi A, Misumi Y, Okamoto S, Ueda A, Ueda M, Obayashi K, Nakamura M, Jono H, Shono M, Asonuma A, Inomata Y, Ando Y
  • Organizer: VIIIth International Symposium on Familial Amyloidotic Polyneuropathy and VIIth International Symposium on Liver Transplantation in Familial Amyloidotic Polyneuropathy
  • Place of Presentation: Kumamoto
  • Year and Date: 20111120-22
• [Presentation] Effect of liver transplantation on clinical manifestations of familial amyloid polyneuropathy (2011)
  • Author(s): Yamashita T, Misumi Y, Okamoto S, Hitahara T, Ueda M, Obayashi K, Nakamura M, Jono H, Shono M, Asonuma K, Inomata Y, Uchino M, Ando Y
  • Organizer: 2011 Biennial Meeting of the Peripheral Nerve Society
  • Place of Presentation: Potomac, Maryland
  • Year and Date: 20110625-29
• [Presentation] 家族性アミロイドポリニューロパチー患者の末梢神経障害に対する肝移植の効果の検討 (2011)
  • Author(s): 山下太郎, 三隅洋平, 大嶋俊範, 植田明彦, 植田光晴, 城野博史, 大林光念, 安東由喜雄, 内野 誠
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 20110518-20
• [Remarks] 熊本大学大学院生命科学研究部神経内科学分野(ホームページ等)
  • URL: http://www2.kuh.kumamoto-u.ac.jp/neurology/
• [Remarks] 熊本大学医学部附属病院神経内科アミロイドーシス診療体制構築事業(ホームページ等)
  • URL: http://www2.kuh.kumamoto-u.ac.jp/amyloidunit/