AlzPathway, an Updated Map of Curated Signaling Pathways: Towards Deciphering Alzheimer’s Disease Pathogenesis

  • Soichi Ogishima
  • Satoshi Mizuno
  • Masataka Kikuchi
  • Akinori Miyashita
  • Ryozo Kuwano
  • Hiroshi Tanaka
  • Jun Nakaya
Part of the Methods in Molecular Biology book series (MIMB, volume 1303)


Alzheimer’s disease (AD) is a complex neurodegenerative disorder in which loss of neurons and synaptic function causes dementia in the elderly. To clarify AD pathogenesis and develop drugs for AD, thousands of studies have elucidated signaling pathways involved. However, knowledge of AD signaling pathways has not been compiled as a pathway map. In this chapter, we introduce the manual construction of a pathway map in AD which we call “AlzPathway”, that comprehensively catalogs signaling pathways in the field of AD. We have collected and manually curated over 100 review articles related to AD, and have built the AD pathway map. AlzPathway is currently composed of thousands of molecules and reactions in neurons, brain blood barrier, presynaptic, postsynaptic, astrocyte, and microglial cells, with their cellular localizations. AlzPathway provides a systems-biology platform of comprehensive AD signaling and related pathways which is expected to contribute to clarification of AD pathogenesis and AD drug development.

Key words

Alzheimer’s disease Systems biology Signaling pathway Pathway map Manual curation AlzPathway Drug discovery 



This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.


  1. 1.
    Alzheimer’s Society (2013) What is Alzheimer’s disease? Last updated Mar 2012Google Scholar
  2. 2.
    Bertram L, McQueen MB, Mullin K et al (2007) Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 39:17–23PubMedCrossRefGoogle Scholar
  3. 3.
    Mizuno S, Iijima R, Ogishima S et al (2012) AlzPathway: a comprehensive map of signaling pathways of Alzheimer’s disease. BMC Syst Biol 6:52PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Funahashi A, Matsuoka Y, Jouraku A et al (2008) Cell Designer 3.5: a versatile modeling tool for biochemical networks. Proc IEEE 96:1254–1265CrossRefGoogle Scholar
  5. 5.
    Laibe C, Le Novère N (2007) MIRIAM resources: tools to generate and resolve robust cross-references in systems biology. BMC Syst Biol 1:58PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Guerreiro R, Wojtas A, Bras J et al (2013) TREM2 variants in Alzheimer’s disease. N Engl J Med 368:117–127PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Jonsson T, Stefansson H, Steinberg S et al (2013) Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med 368:107–116PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Hucka M, Finney A, Sauro HM et al (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19:524–531PubMedCrossRefGoogle Scholar
  9. 9.
    Matsuoka Y, Ghosh S, Kikuchi N, Kitano H (2010) Payao: a community platform for SBML pathway model curation. Bioinformatics 26:1381–1383PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Oda K, Matsuoka Y, Funahashi A, Kitano H (2005) A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol 1:2005.0010PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Oda K, Kitano H (2006) A comprehensive map of the toll-like receptor signaling network. Mol Syst Biol 2:2006.0015PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Calzone L, Gelay A, Zinovyev A et al (2008) A comprehensive modular map of molecular interactions in RB/E2F pathway. Mol Syst Biol 4:173PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Caron E, Ghosh S, Matsuoka Y et al (2010) A comprehensive map of the mTOR signaling network. Mol Syst Biol 6:453PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Le Novère N, Hucka M, Mi H et al (2009) The systems biology graphical notation. Nat Biotechnol 27:735–741PubMedCrossRefGoogle Scholar
  15. 15.
    Smoot ME, Ono K, Ruscheinski J et al (2011) Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27:431–432PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Girvan M, Newman ME (2002) Community structure in social and biological networks. Proc Natl Acad Sci U S A 99:7821–7826PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Fujita KA, Ostaszewski M, Matsuoka Y et al (2013) Integrating pathways of Parkinson’s disease in a molecular interaction map. Mol Neurobiol 49:88–102PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Soichi Ogishima
    • 1
  • Satoshi Mizuno
    • 1
  • Masataka Kikuchi
    • 2
    • 3
  • Akinori Miyashita
    • 2
  • Ryozo Kuwano
    • 2
  • Hiroshi Tanaka
    • 4
  • Jun Nakaya
    • 1
  1. 1.Department of Bioclinical Informatics, Tohoku Medical Megabank OrganizationTohoku UniversityMiyagiJapan
  2. 2.Department of Molecular Genetics, Center for Bioresources, Brain Research InstituteNiigata UniversityNiigataJapan
  3. 3.Research Association for BiotechnologyTokyoJapan
  4. 4.Department of Bioinformatics, Medical Research InstituteTokyo Medical and Dental UniversityTokyoJapan

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