title: Reverse engineering of Alzheimer's disease based on biomarker pathways analysis.
abstract: Alzheimer's disease (AD) poses an increasingly profound problem to society, yet progress toward a genuine understanding of the disease remains worryingly slow. Perhaps, the most outstanding problem with the biology of AD is the question of its mechanistic origins, that is, it remains unclear wherein the molecular failures occur that underlie the disease. We demonstrate how molecular biomarkers could help define the nature of AD in terms of the early biochemical events that correlate with disease progression. We use a novel panel of biomolecules that appears in cerebrospinal fluid of AD patients. As changes in the relative abundance of these molecular markers are associated with progression to AD from mild cognitive impairment, we make the assumption that by tracking their origins we can identify the biochemical conditions that predispose their presence and consequently cause the onset of AD. We couple these protein markers with an analysis of a series of genetic factors and together this hypothesis essentially allows us to redefine AD in terms of the molecular pathways that underlie the disease.
authors.affiliation: Cell Biophysics Group, School of Life Sciences, Faculty of Medicine & Health Sciences, University Park, University of Nottingham, Nottingham, UK.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Richens
authors.affiliation: Humans Genetics Research Group, School of Life Sciences, Faculty of Medicine & Health Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Morgan
authors.affiliation: Cell Biophysics Group, School of Life Sciences, Faculty of Medicine & Health Sciences, University Park, University of Nottingham, Nottingham, UK. Electronic address: paul.oshea@nottingham.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: O'Shea
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D018450:Disease Progression; D066246:ErbB Receptors / Q000502:physiology; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D020932:Nerve Growth Factor / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D010982:Platelet-Derived Growth Factor; D051880:Receptors, Notch; D020932:Nerve Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Alzheimer's disease; Biomarkers; Dementia; Pathways analysis