Analysis of p3-Alc peptides, the novel biomarker for Alzheimer's disease

• Project/Area Number: 24790062
• 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, 薬学研究科(研究院), 助教 (40581012)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); 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: アルツハイマー病

Research Abstract

Alzheimerz's disease (AD) is the most common senile dementia. However, the pathogenesis of AD remains unclear. Moreover, early detection methods and fundamental therapeutic methods for AD are not fully established.
In this study, I detected p3-Alc peptides from CSF samples and plasma samples of AD patients. Our results suggest that alternative processing of multiple gamma-secretase substrates may occur in some AD patients. These finding raise the possibility that the molecular pathogenesis of AD might involve gamma-secretase dysfunction. Measurement of p3-Alc levels may be useful in selecting subjects that might benefit from patient-specific therapy aimed at modulation of gamma-secretase function.

Research Products

• [Journal Article] Increased levels of plasma p3-Alcα35, a major fragment of Alcadeinαbyγ-secretase cleavage, in Alzheimer's disease (2014)
  • Author(s): Omori, C., Kaneko, M., Nakajima, E., Akatsu, H., Waragai, M., Maeda, M., Morishima-Kawashima, M., Saito, Y., Nakaya, N., Taru, H., Yamamoto, T., Asada, T., Hata S., Suzuki T., J-ADNI
  • Journal Title: J. Alzheimer Dis Volume: 39 Pages: 861-870
  • Peer Reviewed
• [Journal Article] Increased levels of plasma p3-Alcα35, a major fragment of Alcadeinα by γ-secretase cleavage, in Alzheimer's disease (2014)
  • Author(s): Omori C, Kaneko M, Nakajima E, Akatsu H, Waragai M, Maeda M, Moroshima-Kawashima M, Saito Y, Nakaya T, Taru H, Yamamoto T, Asada T, Hata S, Suzuki T. for J-ADNI
  • Journal Title: J. Alzheimers Dis Volume: 39 Issue: 4 Pages: 861-870
  • DOI: 10.3233/jad-131610
  • Peer Reviewed
• [Journal Article] Utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy as adjunct techniques for screening and predicting dementia due to Alzheimer's disease in clinical practice (2014)
  • Author(s): Waragai, M., Hata, S., Suzuki, T., Ishii, R., Fujii, C.,Tokuda, T., Arai, A., Ohrui, T., Higuchi, S., Yoshida, M., Igarashi, K., Moriya, M., Iwai, N., Uemura, K.
  • Journal Title: Jounal of Alzheimer's Disease Volume: In press
  • Peer Reviewed
• [Journal Article] Mechanism of intramembrane cleavage of Alcadeins by γ-secretase (2013)
  • Author(s): Piao, Y., Kimura, A., Urano, S., Saito, Y., Taru, H., Yamamoto, T., Hata, S. and Suzuki, T
  • Journal Title: PLoS One Volume: 8 Issue: 4 Pages: e62431-e62431
  • DOI: 10.1371/journal.pone.0062431
  • Peer Reviewed
• [Journal Article] Constitutive Cleavage of the Single-pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1. (2012)
  • Author(s): Chiaki Maruta
  • Journal Title: PLoS One Volume: 7 Issue: 8 Pages: e43058-e43058
  • DOI: 10.1371/journal.pone.0043058
  • Peer Reviewed
• [Journal Article] Membrane-microdomain localization of amyloid β-precursor protein (APP) C-terminal fragments is regulated by phosphorylation of the cytoplasmic Thr668 residue (2012)
  • Author(s): Matsushima T
  • Journal Title: J Biol Chem Volume: 287 Issue: 23 Pages: 19715-19724
  • DOI: 10.1074/jbc.m111.334847
  • Peer Reviewed
• [Journal Article] Multiple γ-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer's disease subjects. (2012)
  • Author(s): Hata S
  • Journal Title: Mol Neurodegener. Volume: 16 Issue: 1 Pages: 16-16
  • DOI: 10.1186/1750-1326-7-16
  • Peer Reviewed
• [Journal Article] Potential utility of soluble p3-alcadeinα plasma levels as a biomarker for sporadic Alzheimer's disease (2012)
  • Author(s): Kamogawa K, Kohara K, Tabara Y, Takita R, Miki T, Konno T, Hata S, Suzuki T
  • Journal Title: J Alzheimers Dis Volume: 31 Issue: 2 Pages: 421-8
  • DOI: 10.3233/jad-2012-120601
  • Peer Reviewed
• [Journal Article] Utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy as adjunct techniques for screening and predicting dementia due to Alzheimer's disease in clinical practice
  • Author(s): Waragai, M., Hata, S., Suzuki, T., Ishii, R., Fujii, C., Tokuda, T., Arai, A., Ohrui, T., Higuchi, S., Yoshida, M., Igarashi, K., Moriya, M., Iwai, N., Uemura, K
  • Journal Title: J. Alzheimer Dis Volume: (in press)
  • Peer Reviewed
• [Presentation] p3-Alc peptide in the CSF and plasma of sporadic Alzheimer's disease patients (2013)
  • Author(s): Hata, S
  • Organizer: Society for Neuroscience annual meeting Neuroscience 2013
  • Place of Presentation: San Diego, USA
• [Presentation] Function of Alcadein and its metabolite, p3-Alc (2013)
  • Author(s): 羽田沙緒里
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] Quantitative alteration of p3-Alc peptides in CSF of Alzheimer's disease patients (2013)
  • Author(s): Hata, S
  • Organizer: Alzheimer's Association International Conference 2013
  • Place of Presentation: Boston, USA
• [Presentation] Quantitative alteration of p3-Alc peptides in CSF of Alzheimer’s disease patients (2013)
  • Author(s): Hata, S., Omori, C., Kaneko, M., Waragai, M., Urakami, K., Taniguchi, M., Ikeuchi, T., Akatsu, H., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2013
  • Place of Presentation: Boston Convention and Exhibition Center (USA)
• [Presentation] Neuron-specific phosphorylation of APP: The roles in APP metabolism and function (2013)
  • Author(s): Suzuki, T., Matsushima, T., Saito, Y., Taru, H., Hata, S.
  • Organizer: Alzheimer's Association International Conference 2013
  • Place of Presentation: Boston Convention and Exhibition Center (USA)
• [Presentation] Quantification of plasma p3-Alcα35 with C-terminal end- specific sELISA system (2013)
  • Author(s): Kaneko,M., Omori, C., Maeda, M., Akatsu, H., Waragai, M., Nakajima, E., Asada, T., Hata, S., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2013
  • Place of Presentation: Boston Convention and Exhibition Center (USA)
• [Presentation] p3-Alc peptide in the CSF and plasma of sporadic Alzheimer’s disease patients. (2013)
  • Author(s): Hata, S., Konno, T., Urakami, K., Ikeuchi, T., Akatsu, H., Suzuki, T.
  • Organizer: Society for Neuroscience annual meeting, Neuroscience 2013
  • Place of Presentation: San Diego Convention Center (USA)
• [Presentation] Expression of novel function of Alcadein intracellular domain. (2013)
  • Author(s): Sobu, U., Takei, N., Hata, S., Suzuki, T.
  • Organizer: y for Neuroscience annual meeting, Neuroscience 2013
  • Place of Presentation: San Diego Convention Center (USA)
• [Presentation] Phosphorylation of APP is not involved in the regulation of APP anterograde transport by kinesin-1. (2013)
  • Author(s): Shiraki, Y., Hata, S., Suzuki, T.
  • Organizer: Society for Neuroscience annual meeting, Neuroscience 2013
  • Place of Presentation: San Diego Convention Center (USA)
• [Presentation] APPとAlcadein代謝におけるApolipoprotein Eの効果 (2013)
  • Author(s): 木村彩乃、羽田沙緒里、道川誠、鈴木利治
  • Organizer: 第18回日本病態プロテアーゼ学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター (大阪）
• [Presentation] Function of Alcadein and its metabolite, p3-Alc (2013)
  • Author(s): 羽田沙緒里、鈴木利治
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜 (神奈川）
  • Invited
• [Presentation] アルツハイマー病患者における血中ｐ３－Ａｌｃα解析 (2013)
  • Author(s): 金子窓香、大森智織、前田雅弘、赤津裕康、藁谷正明、中島悦子、朝田隆、羽田沙緒里、鈴木利治
  • Organizer: 第3回 日本認知症予防学会 学術集会
  • Place of Presentation: 朱鷺メッセ （新潟）
• [Presentation] 脳脊髄液・血液診断マーカーとしてのp3-Alcの解析 (2012)
  • Author(s): 羽田沙緒里
  • Organizer: 第31回日本認知症学会学術集会
  • Place of Presentation: 筑波
• [Presentation] Increased p3-Alc peptides in the CSF and plasma of sporadic Alzheimer's disease patients (2012)
  • Author(s): Hata, S
  • Organizer: Alzheimer's Association International Conference 2012
  • Place of Presentation: Vancouver, Canada
• [Presentation] Increased p3-Alc peptides in the CSF and plasma of sporadic Alzheimer's disease patients. (2012)
  • Author(s): Hata, S., Konno, T., Urakami, K., Ikeuchi, T., Akatsu, H., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2012
  • Place of Presentation: Vancourver Convention Center (Canada)
• [Presentation] Membrane microdomain localization of APP C-terminal fragments regulated by the phosphorylation at cytoplasmic Thr668 residue. (2012)
  • Author(s): Matsushima, T., Saito, Y., Nishimura, M., Kimura, N., Hata, S., Suzuki, T.
  • Organizer: Alzheimer's Association International Conference 2012
  • Place of Presentation: Vancourver Convention Center (Canada)
• [Presentation] Transplocation of APP cytoplasmic fragment regulated by phosphorylation of Thr668 residue. NANOSYMPOSIUM “Alzheimer’s disease and other dementia: Abeta Metabolism (2012)
  • Author(s): Suzuki, T., Matsushima, T., Hata, S., Yamamoto, T., Saito, Y.
  • Organizer: Society for Neuroscience annual meeting, Neuroscience 2012
  • Place of Presentation: Ernest N. Morial Convention Center (USA)
• [Presentation] Mechanism of intramembrane cleavage of neural Alcadein proteins by γ-secretase. (2012)
  • Author(s): Piao, Y., Hata, S., Suzuki, T.
  • Organizer: Society for Neuroscience annual meeting, Neuroscience 2012
  • Place of Presentation: Ernest N. Morial Convention Center (USA)
• [Presentation] Role of Apolipoprotein E on Alcadeins metabolism. (2012)
  • Author(s): Kimura, A., Hata, S., Suzuki, T.
  • Organizer: Society for Neuroscience annual meeting, Neuroscience 2012
  • Place of Presentation: Ernest N. Morial Convention Center (USA)
• [Presentation] 血中p3-Alcαの定量によるアルツハイマー病のγセクレターゼ切断変化解析 (2012)
  • Author(s): 大森智織、池内健、松原 悦朗、朝田隆、羽田沙緒里、鈴木利治
  • Organizer: 第17回日本病態プロテアーゼ学会学術集会
  • Place of Presentation: オークラアクトシティホテル浜松 (静岡）
• [Presentation] p3-Alcのアルツハイマー病早期診断マーカーとしての有用性の検証 (2012)
  • Author(s): 金子窓香、羽田沙緒里、鈴木利治
  • Organizer: 第17回日本病態プロテアーゼ学会学術集会
  • Place of Presentation: オークラアクトシティホテル浜松 （静岡）
• [Presentation] γセクレターゼによるAlcadeinの膜内切断は、膜脂質組成によって変化する -孤発性アルツハイマー病の発症機構と予防への分子機構- (2012)
  • Author(s): 朴懿、羽田沙緒里、鈴木利治
  • Organizer: 第2回 日本認知症予防学会 学術集会
  • Place of Presentation: 北九州国際会議場 （福岡）
• [Presentation] 脳脊髄液・血液診断マーカーとしてのp3-Alcの解析 (2012)
  • Author(s): 羽田沙緒里、大森智織、浦上克哉、池内健、赤津裕康、朝田隆、鈴木利治
  • Organizer: 第31回日本認知症学会学術集会
  • Place of Presentation: つくば国際会議場 （茨城）
• [Presentation] Alcadein代謝産物による機能発現 (2012)
  • Author(s): 江波綾佳、朴懿、森島真帆、羽田沙緒里、鈴木利治
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡 （福岡）
• [Presentation] gamma-secretaseによるAlcadeinの膜内切断と孤発性アルツハイマー病の発症機構の解明 (2012)
  • Author(s): Yi Piao、羽田沙緒里、鈴木利治
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡（福岡）
• [Presentation] ヒト型Apolipoprotein EノックインマウスにおけるAlcadein代謝の解析 (2012)
  • Author(s): 木村彩乃、羽田沙緒里、道川誠、鈴木利治
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡（福岡）
• [Presentation] Alcadeinのリン酸化 (2012)
  • Author(s): 蘇武佑里子、古郡慶子、森島真帆、羽田沙緒里、鈴木利治
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡（福岡）
• [Remarks]
  • URL: http://www.pharm.hokudai.ac.jp/shinkei/index.html
• [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] 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