Alzheimer's disease-related peptides as a biomarker for diagnosis in early stage Alzheimer's disease

• Project/Area Number: 15K18854
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: HATA Saori 北海道大学, 薬学研究院, 助教 (40581012)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: アルツハイマー病 / バイオマーカー

Outline of Final Research Achievements

Alzheimer’s disease (AD) is the most common senile dementia. AD pathology in the brain is estimated to progress over years prior to detectible cognitive impairment. Biomarkers for early detection of AD may be necessary to develop effective AD treatment. In this study, we identified p3-Alc peptides as a useful indicator of AD pathogenesis, and developed the sELISA system of the peptides. Quantitative analyses of p3-Alc peptides indicate that p3-Alc may be useful biomarker for early diagnosis of AD.

Research Products

• [Journal Article] Facilitation of brain mitochondrial activity by 5-aminolevulinic acid in a mouse model of Alzheimer's disease (2017)
  • Author(s): Chiori Omori, Rika Motodate, Yuzuha Shiraki, Kyoko Chiba, Yuriko Sobu, Ayano Kimura, Tadashi Nakaya, Hikaru Kondo, Satoshi Kurumiya, Toru Tanaka, Kazuo Yamamoto, Motowo Nakajima, Toshiharu Suzuki and Saori Hata
  • Journal Title: Nutritional neuroscience Volume: 印刷中 Issue: 9 Pages: 538-546
  • DOI: 10.1080/1028415x.2016.1199114
  • Peer Reviewed / Open Access
• [Journal Article] Expression and localization of X11 family proteins in neurons (2016)
  • Author(s): Motodate, R., Saito, Y., Hata, S., Suzuki, T.
  • Journal Title: Brain Res Volume: 1646 Pages: 227-234
  • DOI: 10.1016/j.brainres.2016.05.054
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Specific triazine herbicides induce amyloidβ42 production. (2016)
  • Author(s): Portlius E, Durieu E, Bodin M, Cam M, Pannee J, Leuxe C, Mabondzo A, Oumata N, Galons H, Lee J-Y, Chang Y-T, Stuber K, Koch P, Fontanine G, Potier M, Manouspoulou A, Garbis S, Covaci A, VanDam D, De Deyn P, Karg F, Flajolet M, Omori C, Hata S, Suzuki T, Blennow K, Zetteberg H, and Meijer L
  • Journal Title: J. Alzheimer Dis Volume: 54 Issue: 4 Pages: 1593-1605
  • DOI: 10.3233/jad-160310
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Alternative Selection of BACE1 Cleavage Sites in APP Harboring Protective And Pathogenic Mutations Within the Aβ Sequence (2016)
  • Author(s): Kimura, A., Hata, S., Suzuki, T
  • Journal Title: J. Biol. Chem. Volume: 291 Issue: 46 Pages: 24041-24053
  • DOI: 10.1074/jbc.m116.744722
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cytoplasmic Fragment of Alcadein α Generated by Regulated Intramembrane Proteolysis Enhances Amyloid β-Protein Precursor (APP) Transport into the Late Secretory Pathway and Facilitates APP Cleavage (2015)
  • Author(s): Norio Takei, Yuriko Sobu, Ayano Kimura, Satomi Urano, Yi Piao, Yoichi Araki, Hidenori Taru, Tohru Yamamoto, Saori Hata, Tadashi Nakaya, Toshiharu Suzuki
  • Journal Title: Journal of Biological Chemistry Volume: 290 Issue: 2 Pages: 987-995
  • DOI: 10.1074/jbc.m114.599852
  • Peer Reviewed / Open Access
• [Journal Article] Stabilization of intracellular trafficking and metabolism of amyloid β-protein precursor and Alcadein β by apolipoprotein E (2015)
  • Author(s): Kimura, A., Hata, S., Suzuki, T.
  • Journal Title: FEBS Lett Volume: 589 Issue: 18 Pages: 2394-2400
  • DOI: 10.1016/j.febslet.2015.07.017
  • NAID: 120005828463
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Level of p3-Alcβ Peptides Alter in CSF of AD Patients (2017)
  • Author(s): Hata, S., Kimura, A., Waragai, M., Ikeuchi, T., Martins, RN., Kimura, N.,Nishimura, M., Suzuki,T.
  • Organizer: Alzheimer's Association International Conference 2017
  • Place of Presentation: ロンドン（イギリス）
  • Year and Date: 2017-07-16
  • Int'l Joint Research
• [Presentation] Different cargo receptors, APP and Alcα, transport the same cargos cooperatively through the identical vesicular transport pathway (2016)
  • Author(s): Shiraki, Y., Chiba, K., Hata, S., Suzuki T.
  • Organizer: The American Society for Cell Biology, Annual Meeting
  • Place of Presentation: サンフランシスコ（アメリカ）
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] Multiple phosphorylations of Alcadeinα regulates interaction with kinesin-1. (2016)
  • Author(s): Sobu, Y, Hata, S., Suzuki, T.
  • Organizer: The American Society for Cell Biology, Annual Meeting
  • Place of Presentation: サンフランシスコ（アメリカ）
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] Mechanism that BACE1 alternates the cleaving sites of human APP (2016)
  • Author(s): Suzuki, T., Kimura, A., Hata, S.
  • Organizer: Society for Neuroscience annual meeting, Neuroscience 2016
  • Place of Presentation: サンディエゴ（アメリカ）
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Alternative cleavage mechanism of human BACE1 (2016)
  • Author(s): Suzuki, T., Kimura A., Hata, S.
  • Organizer: Alzheimer's Association International Conference 2016
  • Place of Presentation: トロント（カナダ）
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] Increase of p3-Alcα38 to p3-Alcα35, products by γ-secretase cleavage, in CSF of AD patients (2016)
  • Author(s): Omori, C., Hata, S., Waragai, M., Yamamoto, K., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2016
  • Place of Presentation: トロント（カナダ）
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] Altered cellular cholesterol levels cause aberrant γ-secretase cleavages ofAPP and Alcadeinα (2016)
  • Author(s): Hu, A., Piao, Y., Hata, S., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2016
  • Place of Presentation: トロント（カナダ）
  • Year and Date: 2016-07-24
  • Int'l Joint Research
• [Presentation] Alteration of membrane microlocalization and γ-secretase cleavages in sporadic Alzheimer's disease. (2016)
  • Author(s): Hata, S., Piao, Y., Hu, A., Nishimura, M., Suzuki, T.
  • Organizer: The 4th International Conference on Molucular Neurodegeneration
  • Place of Presentation: ソウル（韓国）
  • Year and Date: 2016-05-09
  • Int'l Joint Research
• [Presentation] Membrane lipid composition and γ-secretase cleavage of Alzheimer’s disease-related proteins (2015)
  • Author(s): 羽田沙緒里、朴 懿、西村正樹、鈴木利治
  • Organizer: 第88回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド、兵庫県神戸市
  • Year and Date: 2015-12-01
• [Presentation] Functional and regulation of APP and Alcadeinα cargos transported by kinesin-1 in neuron (2015)
  • Author(s): Shiraki, Y., Chiba, K., Hata, S., Suzuki, T.
  • Organizer: Society for Neuroscience annual meeting, Neuroscience 2015
  • Place of Presentation: McCormick Place, Chicago, USA
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Association of Alcadeinα with kinesin light chain is regulated by phosphorylations at cytoplasmic acidic region (2015)
  • Author(s): Sobu,Y.,Hata,S.,Suzuki,T
  • Organizer: Society for Neuroscience annual meeting, Neuroscience 2015
  • Place of Presentation: McCormick Place, Chicago, USA
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] AlcadeinとX11LによるAPP代謝制御 (2015)
  • Author(s): 川原聡史、後藤直也、羽田沙緒里、山本 融、鈴木利治
  • Organizer: 第34回日本認知症学会学術集会
  • Place of Presentation: リンクステーションホール青森、青森県青森市
  • Year and Date: 2015-10-02
• [Presentation] 膜コレステロール含量に依存したγセクレターゼによる基質切断変化 (2015)
  • Author(s): 胡安琪、朴懿、羽田沙緒里、西村正樹、鈴木利治
  • Organizer: 第34回日本認知症学会学術集会
  • Place of Presentation: リンクステーションホール青森、青森県青森市
  • Year and Date: 2015-10-02
• [Presentation] p3-Alcの検出によるγセクレターゼ切断解析 (2015)
  • Author(s): 羽田沙緒里、大森智織、藁谷正明、鈴木利治
  • Organizer: 第34回日本認知症学会学術集会
  • Place of Presentation: リンクステーションホール青森、青森県青森市
  • Year and Date: 2015-10-02
• [Presentation] p3-Alcα分子種のアルツハイマー病バイオマーカー有用性の検証 (2015)
  • Author(s): 大森智織、羽田沙緒里、藁谷正明、前田雅弘、立花太郎、Laurent Meijer、山本一夫、鈴木利治
  • Organizer: 第5回日本認知症予防学会 学術集会
  • Place of Presentation: 神戸国際会議場、兵庫県神戸市
  • Year and Date: 2015-09-25
• [Presentation] 孤発性アルツハイマー病における膜マイクロドメインのγセクレターゼ活性変化 (2015)
  • Author(s): 羽田沙緒里、朴 懿、西村正樹、鈴木利治
  • Organizer: 第5回日本認知症予防学会 学術集会
  • Place of Presentation: 神戸国際会議場、兵庫県神戸市
  • Year and Date: 2015-09-25
• [Presentation] Kinesine-1 cargo receptor APP and Alcadeinα transport different type of vesicular cargo to the axonal terminal (2015)
  • Author(s): Shiraki, Y., Chiba, K., Hata, S., Suzuki, T
  • Organizer: 25th Meeting of the International Society for Neurochemistry
  • Place of Presentation: Cairns Convention Center, Cairns, Australia
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] Regulation of Alcadeinα association with kinesin-1 by phosphorylation of the cytoplasmic region (2015)
  • Author(s): Sobu,Y.,Hata,S.,Suzuki,T.
  • Organizer: 25th Meeting of the International Society for Neurochemistry
  • Place of Presentation: Cairns Convention Center, Cairns, Australia
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] Regulation of axonal transport of APP cargos by kinesin-1 (2015)
  • Author(s): Suzuki, T., Chiba, K., Hata, S
  • Organizer: 25th Meeting of the International Society for Neurochemistry
  • Place of Presentation: Cairns Convention Center, Cairns, Australia
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] 膜脂質組成の変化によるAPPとAlcadeinの膜内切断機構の解析 (2015)
  • Author(s): 胡安琪、朴懿、羽田沙緒里、鈴木利治
  • Organizer: 第52回日本生化学会北海道支部例会
  • Place of Presentation: 北海道大学 フロンティア応用科学研究棟、北海道札幌市
  • Year and Date: 2015-07-17
• [Presentation] γセクレターゼの基質切断解析による孤発性アルツハイマー病発症機構の解明 (2015)
  • Author(s): 羽田沙緒里、鈴木利治
  • Organizer: 第52回日本生化学会北海道支部例会
  • Place of Presentation: 北海道大学 フロンティア応用科学研究棟、北海道札幌市
  • Year and Date: 2015-07-17
• [Remarks] 北海道大学薬学部 神経科学研究室
  • URL: http://www.pharm.hokudai.ac.jp/shinkei/index.html
• [Remarks] http://www.pharm.hokudai.ac.jp/shinkei/index.html