title: Drivers: A Biologically Contextualized, Cross-Inferential View of the Epidemiology of Neurodegenerative Disorders.
abstract: BACKGROUND
  Sutherland et al. (2011) suggested that, instead of risk factors for single neurodegenerative disorders (NDDs), there was a need to identify specific "drivers", i.e., risk factors with impact on specific deposits, such as amyloid-β, tau, or α-synuclein, acting across entities.
  
  
  OBJECTIVE
  Redefining drivers as "neither protein/gene- nor entity-specific features identifiable in the clinical and general epidemiology of conformational NDDs (CNDDs) as potential footprints of templating/spread/transfer mechanisms", we conducted an analysis of the epidemiology of ten CNDDs, searching for patterns.
  
  
  RESULTS
  We identified seven potential drivers, each of which was shared by at least two CNDDs: 1) an age-at-exposure-related susceptibility to Creutzfeldt-Jakob disease (CJD) and several late-life CNDDs; 2) a relationship between age at onset, survival, and incidence; 3) shared genetic risk factors for CJD and late-life CNNDs; 4) partly shared personal (diagnostic, educational, behavioral, and social risk factors) predating clinical onset of late-life CNDDs; 5) two environmental risk factors, namely, surgery for sporadic CJD and amyotrophic lateral sclerosis, and Bordetella pertussis infection for Parkinson's disease; 6) reticulo-endothelial system stressors or general drivers (andropause or premenopausal estrogen deficiency, APOEɛ4, and vascular risk factors) for late-life CNDDs such as dementia/Alzheimer's disease, type-2 diabetes mellitus, and some sporadic cardiac and vascular degenerative diseases; and 7) a high, invariant incidence ratio of sporadic to genetic forms of mid- and late-life CNDDs, and type-2 diabetes mellitus.
  
  
  CONCLUSIONS
  There might be a systematic epidemiologic pattern induced by specific proteins (PrP, TDP-43, SOD1, α-synuclein, amyloid-β, tau, Langerhans islet peptide, and transthyretin) or established combinations of these.
authors.affiliation: Department of Applied Epidemiology, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: de Pedro-Cuesta
authors.affiliation: Department of Applied Epidemiology, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-Martín
authors.affiliation: Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.|Alzheimer Disease Research Unit, CIEN Foundation, Queen Sofia Foundation Alzheimer Center, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rábano
authors.affiliation: Department of Applied Epidemiology, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Alcalde-Cabero
authors.affiliation: Department of Applied Epidemiology, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: José García López
authors.affiliation: Department of Applied Epidemiology, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Almazán-Isla
authors.affiliation: Department of Applied Epidemiology, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Ruiz-Tovar
authors.affiliation: Department of Applied Epidemiology, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.
authors.forename: Maria-José
authors.initials: MJ
authors.lastname: Medrano
authors.affiliation: Department of Applied Epidemiology, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Avellanal
authors.affiliation: Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.|Chronic Disease Programme, Carlos III Institute of Health, Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Calero
authors.affiliation: Consortium for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.|Alzheimer Disease Research Unit, CIEN Foundation, Queen Sofia Foundation Alzheimer Center, Madrid, Spain.|Chronic Disease Programme, Carlos III Institute of Health, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Calero
mesh_terms: D000367:Age Factors; D000375:Aging; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D007562:Creutzfeldt-Jakob Syndrome / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D004777:Environment; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D019636:Neurodegenerative Diseases / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D010551:Personality; D012307:Risk Factors; D014652:Vascular Diseases / Q000453:epidemiology* / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Amyloid; epidemiology; methods; neurodegeneration; risk factors