Searching for autoantibodies related Alzheimer disease by proteomics and protein array system

• Project/Area Number: 24591256
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Gifu University
• Principal Investigator: INUZUKA Takashi 岐阜大学, 医学(系)研究科(研究院), 教授 (50184734)
• Co-Investigator(Kenkyū-buntansha): KIMURA Akio 岐阜大学, 大学院医学系研究科, 准教授 (00362161) ; YANO Takeo 三重大学, 地域イノベーション学研究科, 教授 (00569197)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アルツハイマー型認知症 / 抗血管内皮抗体 / 抗神経抗体 / バイオマーカー / プロテオミクス / 二次元ブロット法 / 質量分析 / 抗Tom40抗体

Outline of Final Research Achievements

We identified novel autoantibodies in serum samples from patients with Alzheimer’s diseases. To identify these novel antibodies, we employed two-dimensional immunoblotting using human neuroblastoma cells, human brain microvascular endothelial cells, or rat brain homogenate as the antigen source. As a result, we identified autoantibodies against Phosphatidylinositol transfer protein alpha isoform and Mitochondrial import receptor subunit TOM40 homolog in sera from patients with Alzheimer’s diseases. There are several reports describing that these autoantigens may be associated with Alzheimer’s diseases. Further studies are needed to establish whether our identified autoantibodies could be useful biomarkers of Alzheimer’s diseases.

Research Products

• [Journal Article] Identification of target antigens of antiendothelial cell antibodies against human brain microvascular endothelial cells in healthy subjects. (2015)
  • Author(s): Kimura A, Sakurai T, Yoshikura N, Koumura A, Hayashi Y, Ohtaki H, Chousa M, Seishima M, Inuzuka T.
  • Journal Title: Curr Neurovasc Res. Volume: 12 Pages: 25-30
  • Peer Reviewed
• [Journal Article] B-cell-activating factor belonging to the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) levels in cerebrospinal fluid of patients with meningoencephalitis. (2015)
  • Author(s): Kimura A, Yoshikura N, Koumura A, Hayashi Y, Inuzuka T.
  • Journal Title: J Neurol Sci. Volume: 未定 Issue: 1-2 Pages: 79-83
  • DOI: 10.1016/j.jns.2015.03.036
  • Peer Reviewed
• [Journal Article] Corticosteroid therapy in a patient with cerebral amyloid angiopathy-related inflammation. (2013)
  • Author(s): Kimura A, Sakurai T, Yoshikura N, Hayashi Y, Takemura M, Takahashi H, Inuzuka T.
  • Journal Title: Journal of Neuroinflammation Volume: 10 Issue: 1 Pages: 39-39
  • DOI: 10.1186/1742-2094-10-39
  • Peer Reviewed
• [Journal Article] ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis. (2013)
  • Author(s): Tanaka H.. Shimazawa M., Takata M., Kaneko H., Tsuruma K., Ikeda T., Warita H., Aoki M., Yamada M., Takahashi H., Hozumi I., Minatsu H., Inuzuka T. and Hara H.
  • Journal Title: Journal of Neurology Volume: (Epub ahead of print) Issue: 7 Pages: 1782-1797
  • DOI: 10.1007/s00415-013-6877-3
  • Peer Reviewed
• [Journal Article] Is there a difference in gastric emptying between myotonic dystrophy type 1 patients with and without gastrointestinal symptoms? (2013)
  • Author(s): Tanaka Y, Kato T, Nishida H, Yamada M, Koumura A, Sakurai T, Hayashi Y, Kimura A, Hozumi I, Araki H, Murase M, Nagaki M, Moriwaki H, Inuzuka T.
  • Journal Title: Journal of Neurology Volume: 印刷中 Issue: 6 Pages: 1611-1616
  • DOI: 10.1007/s00415-013-6842-1
  • Peer Reviewed
• [Journal Article] Anti-Endothelial Cell Antibodies in Patients with Cerebral Small Vessel Disease. (2012)
  • Author(s): Kimura A, Sakurai T, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Ohtaki H, Chousa M, Takemura M, Seishima M, Inuzuka T.
  • Journal Title: Current Neurovascular Research Volume: 9 Issue: 4 Pages: 296-301
  • DOI: 10.2174/156720212803530726
  • Peer Reviewed
• [Journal Article] Antibodies against the tom40 subunit of the translocase of the outer mitochondrial membrane complex and cognitive impairment in Alzheimer's disease (2012)
  • Author(s): Kimura A, Sakurai T, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Ohtaki H, Chousa M, Takemura M, Seishima M, Inuzuka T
  • Journal Title: Journal of Alzheimer's Disease Volume: 29 Issue: 2 Pages: 373-377
  • DOI: 10.3233/jad-2011-111343
  • Peer Reviewed
• [Journal Article] Elevated anti-heat shock protein 60 antibody titer is related to white matter hyperintensities. (2012)
  • Author(s): Kimura A, Sakurai T, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Takemura M, Seishima M, Inuzuka T
  • Journal Title: Journal of Stroke and Cerebrovascular Diseases Volume: 21 Issue: 4 Pages: 305-309
  • DOI: 10.1016/j.jstrokecerebrovasdis.2010.09.003
  • Peer Reviewed
• [Journal Article] Peduncular hallucinations in brainstem encephalitis drawn by a patient. (2012)
  • Author(s): Hayashi Y, Yoshikura N, Kimura A, Inuzuka T.
  • Journal Title: Neurology Volume: 79 Issue: 15 Pages: 1625-1625
  • DOI: 10.1212/wnl.0b013e31826e2673
  • Peer Reviewed
• [Journal Article] Is there delayed gastric emptying in patients with multiple system atrophy? An analysis using the (13)C-acetate breath test. (2012)
  • Author(s): Tanaka Y, Kato T, Nishida H, Yamada M, Koumura A, Sakurai T, Hayashi Y, Kimura A, Hozumi I, Araki H, Murase M, Nagaki M, Moriwaki H, Inuzuka T.
  • Journal Title: Journal of Neurology Volume: 259 Issue: 7 Pages: 1448-1452
  • DOI: 10.1007/s00415-011-6372-7
  • Peer Reviewed
• [Journal Article] L-MPZ, a novel isoform of myelin P0, is produced by stop codon readthrough. (2012)
  • Author(s): Yamaguchi Y, Hayashi A, Campagnoni CW, Kimura A, Inuzuka T, Baba H.
  • Journal Title: The Journal of Biological Chemistry Volume: 287 Issue: 21 Pages: 17765-17776
  • DOI: 10.1074/jbc.m111.314468
  • Peer Reviewed
• [Journal Article] Late-onset Patients with Sporadic Amyotrophic Lateral Sclerosis in Japan have a Higher Progression Rate of ALSFRS-R at the Time of Diagnosis (2012)
  • Author(s): Tanaka Y, Yoshikura N, Harada N, Yamada M, Koumura A, Sakurai T, Hayashi Y, Kimura A, Hozumi I, Inuzuka T.
  • Journal Title: Internal Medicine Volume: 51 Issue: 6 Pages: 579-584
  • DOI: 10.2169/internalmedicine.51.6148
  • NAID: 130002061913
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Presentation] 脳アミロイドアンギオパチー関連炎症および高齢者における抗Aβ-40抗体の特異性の検討 (2015)
  • Author(s): 木村暁夫、竹村正男、吉倉延亮、竹腰 顕、安西将大、瀬川 一、原田斉子、香村彰宏、林 祐一、犬塚 貴
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20 – 2015-05-23
• [Presentation] 自己免疫性神経疾患における抗神経抗体・抗血管内皮抗体に関する検討 (2014)
  • Author(s): 木村暁夫、櫻井岳郎、吉倉延亮、原田斉子、香村彰宏、林 祐一、犬塚 貴
  • Organizer: 第26回日本神経免疫学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2014-09-04 – 2014-09-05
• [Presentation] 膀胱癌合併傍腫瘍性小脳失調症患者における抗神経抗体の検討 (2014)
  • Author(s): 香村彰宏、木村暁夫、吉倉延亮、林 祐一、犬塚 貴
  • Organizer: 第26回日本神経免疫学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2014-09-04 – 2014-09-05
• [Presentation] 脳アミロイドアンギオパチー関連炎症における臨床および髄液所見の検討 (2014)
  • Author(s): 吉倉延亮、木村暁夫、竹腰 顕、瀬川 一、原田斉子、香村彰宏、林 祐一、
  • Organizer: 第26回日本神経免疫学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2014-09-04 – 2014-09-05
• [Presentation] 多発性硬化症患者における髄液中抗神経抗体の検討 (2014)
  • Author(s): 木村暁夫、吉倉延亮、原田斉子、香村彰宏、林 祐一、犬塚 貴
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] アルツハイマー型認知症におけるmicrobleedと臨床所見との関連性の検討 (2014)
  • Author(s): 吉倉延亮、木村暁夫、安西将大、竹腰 顕、原田斉子、香村彰宏、林 祐一、
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-21 – 2014-05-24
• [Presentation] CAA関連炎症・血管炎に対するステロイド治療と髄液マーカーの検索 (2013)
  • Author(s): 木村暁夫、吉倉延亮、原田斉子、香村彰宏、林 祐一、犬塚 貴
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] 自己免疫性中枢性神経疾患患者における血清BAFF, APRIL値の検討 (2013)
  • Author(s): 吉倉延亮、木村暁夫、原田斉子、香村彰宏、林 祐一、犬塚 貴
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] 亜急性小脳失調症における新規抗神経抗体の同定 (2013)
  • Author(s): 香村彰宏、木村暁夫、吉倉延亮、原田斉子、林 祐一、犬塚 貴
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] 自己抗体関連脳炎における髄液中BAFF,APRIL値の検討 (2013)
  • Author(s): 吉倉延亮、木村暁夫、原田斉子、香村彰宏、林 祐一、犬塚 貴
  • Organizer: 第25回日本神経免疫学会学術集会
  • Place of Presentation: 下関海峡タワー
• [Presentation] Pure motor chronic inflammatory demyelinating polyneuropathy (2013)
  • Author(s): Kimura A, Koumura A, Sakurai T, Hayashi Y, Inuzuka T.
  • Organizer: The 65th American Academy of Neurology
  • Place of Presentation: San Diego, USA
• [Presentation] Anti-endotherial cell antibodieis in patients with Alzheimar doiseases (2012)
  • Author(s): Kimura A, Sakurai T, Yamada M, Koumura A, Hayashi Y, Tanaka Y, Hozumi I, Ohtaki H, Chousa M, Inuzuka T.
  • Organizer: The 64th American Academy of Neurology
  • Place of Presentation: New Orleans, USA
• [Presentation] 自己免疫介在性脳炎・脳症における新規自己抗体の同定 (2012)
  • Author(s): 木村暁夫、櫻井岳郎、吉倉延亮、原田斉子、香村彰宏、林 祐一、犬塚 貴
  • Organizer: 第53回日本神経学会
  • Place of Presentation: 東京