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

2013 Fiscal Year Final Research Report

• 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
• 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
  • DOI: 10.3223/JAD-131610
  • Peer Reviewed
• [Journal Article] Mechanism of intramembrane cleavage of Alcadeins by?-secretase (2013)
  • Author(s): Piao, Y., Kimura, A., Urano, S., Saito, Y., Taru, H., Yamamoto, T., Hata, S., Suzuki, T
  • Journal Title: PLoS ONE Volume: 8 Pages: e62431
  • DOI: 10.1371/journal.pone.0062431
  • Peer Reviewed
• [Journal Article] Constitutive cleavage of the single-pass transmembrane protein Alcadeinαprevents aberrant peripheral retention of Kinesin-1 (2012)
  • Author(s): Maruta, C., Saito, Y., Hata, S., Gotoh, N., Suzuki, T., Yamamoto, T
  • Journal Title: PLoS ONE Volume: 7 Pages: e43058
  • DOI: 10.1371/journal.pone.0043058
  • Peer Reviewed
• [Journal Article] Membrane-microdomain localization of amyloid?-precursor protein (APP) C-terminal fragments is regulated by phosphorylation of cytoplasmic Thr668 residue (2012)
  • Author(s): Matsushima, T., Saito, Y., Eliott, J. E., Iijima-Ando, K., Nishimura, M., Kimura, N., Hata, S., Yamamoto, T., Nakaya, T., Suzuki, T
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 19715-17924
  • DOI: 10.1074/jbc.M111.334847
  • Peer Reviewed
• [Journal Article] Multiple?-secretase product peptides are coordinately increased in concentration in the CSF of a subpopulation of sporadic Alzheimer's disease subjects (2012)
  • Author(s): Hata, S., Taniguchi, M., Piao, Y., Ikeuchi, T., Fagan, A. M., Holtzman, D. M., Bateman, R., Gandy, S., Urakami, K., Suzuki, T., J-ADNI
  • Journal Title: Mol. Neurodegener Volume: 7 Pages: 16
  • DOI: 10.1186/1750-1326-7-16
  • Peer Reviewed
• [Journal Article] Utility of plasma levels of soluble p3-Alcadeinαas 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. Alzheimer Dis Volume: 31 Pages: 421-428
  • 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
  • Year and Date: 20131109-13
• [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
  • Year and Date: 20130911-13
• [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
  • Year and Date: 20130713-18
• [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
  • Year and Date: 20121026-28
• [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
  • Year and Date: 20120714-19
• [Remarks]
  • URL: http://www.pharm.hokudai.ac.jp/shinkei/index.html