title: Unraveling the mechanistic complexity of Alzheimer's disease through systems biology.
abstract: Alzheimer's disease (AD) is a complex, multifactorial disease that has reached global epidemic proportions. The challenge remains to fully identify its underlying molecular mechanisms that will enable development of accurate diagnostic tools and therapeutics. Conventional experimental approaches that target individual or small sets of genes or proteins may overlook important parts of the regulatory network, which limits the opportunity of identifying multitarget interventions. Our perspective is that a more complete insight into potential treatment options for AD will only be made possible through studying the disease as a system. We propose an integrative systems biology approach that we argue has been largely untapped in AD research. We present key publications to demonstrate the value of this approach and discuss the potential to intensify research efforts in AD through transdisciplinary collaboration. We highlight challenges and opportunities for significant breakthroughs that could be made if a systems biology approach is fully exploited.
authors.affiliation: Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Laboratory of Molecular Neuroscience, Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia; Department of Molecular Neuroscience, Institute of Neurology, University College of London, London, UK. Electronic address: jennifer.rollo@sydney.edu.au.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Rollo
authors.affiliation: Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Nahid
authors.initials: N
authors.lastname: Banihashemi
authors.affiliation: Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; School of Mathematics and Statistics, University of Sydney, Sydney, NSW, Australia.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Vafaee
authors.affiliation: Rothamsted Research, Harpenden, UK.
authors.forename: John W
authors.initials: JW
authors.lastname: Crawford
authors.affiliation: Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; School of Physics, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Kuncic
authors.affiliation: Laboratory of Molecular Neuroscience, Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia; Discipline of Biomedical Science, School of Medical Sciences, Sydney Medical School, The University of Sydney, Lidcombe, NSW, Australia.
authors.forename: R M Damian
authors.initials: RM
authors.lastname: Holsinger
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D060066:Protein Interaction Maps; D049490:Systems Biology / Q000379:methods*
keywords: Complex systems; Computational modeling; Holistic; Integrative; Risk genes; Transdisciplinary research