%0 Journal Article %J J Alzheimers Dis %D 2016 %T Drivers: A Biologically Contextualized, Cross-Inferential View of the Epidemiology of Neurodegenerative Disorders. %A de Pedro-Cuesta, Jesús %A Martínez-Martín, Pablo %A Rábano, Alberto %A Alcalde-Cabero, Enrique %A José García López, Fernando %A Almazán-Isla, Javier %A Ruiz-Tovar, María %A Medrano, Maria-José %A Avellanal, Fuencisla %A Calero, Olga %A Calero, Miguel %K Age Factors %K Aging %K Amyloid Precursor Protein Secretases %K Apolipoproteins E %K Aspartic Acid Endopeptidases %K Creutzfeldt-Jakob Syndrome %K Environment %K Female %K Humans %K Incidence %K Male %K Neurodegenerative Diseases %K Personality %K Risk Factors %K Vascular Diseases %X

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.

OBJECTIVES AND METHODS: 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.

CONCLUSION: 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.

%B J Alzheimers Dis %V 51 %P 1003-22 %8 2016 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/26923014?dopt=Abstract %R 10.3233/JAD-150884