Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/12767
Drivers: A Biologically Contextualized, Cross-Inferential View of the Epidemiology of Neurodegenerative Disorders.
Pedro-Cuesta, Jesus de ISCIII | Martinez-Martin, Pablo ISCIII | Rábano, Alberto | Alcalde-Cabero, Enrique ISCIII | Garcia Lopez, Fernando Jose ISCIII | Almazan-Isla, Javier ISCIII | Ruiz-Tovar, María ISCIII | Medrano, Maria-José ISCIII | Avellanal, Fuencisla ISCIII | Calero, Olga ISCIII | Calero, Miguel ISCIII
J Alzheimers Dis . 2016;51(4):1003-22
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. 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. 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. 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.
Aging | Environment | Age Factors | Amyloid Precursor Protein Secretases | Apolipoproteins E | Aspartic Acid Endopeptidases | Creutzfeldt-Jakob Syndrome | Female | Humans | Incidence | Male | Neurodegenerative Diseases | Personality | Risk Factors | Vascular Diseases
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