2026-08-05T11:42:09Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/127672025-06-23T16:40:30Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19608col_20.500.12105_19617
Repisalud
author
Pedro-Cuesta, Jesus de
author
Martínez-Martín, Pablo
author
Rábano, Alberto
author
Alcalde-Cabero, Enrique
author
Garcia Lopez, Fernando Jose
author
Almazan-Isla, Javier
author
Ruiz-Tovar, Maria
author
Medrano, Maria Jose
author
Avellanal, Fuencisla
author
Calero, Olga
author
Calero, Miguel
funder
Instituto de Salud Carlos III
2021-04-24T09:39:27Z
2021-04-24T09:39:27Z
2016
J Alzheimers Dis . 2016;51(4):1003-22
10.3233/JAD-150884
1875-8908
Journal of Alzheimer's disease : JAD
26923014
http://hdl.handle.net/20.500.12105/12767
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.
eng
Amyloid
Epidemiology
Methods
Neurodegeneration
Risk factors
Drivers: A Biologically Contextualized, Cross-Inferential View of the Epidemiology of Neurodegenerative Disorders
research article
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DriversABiologicallyContextualized_2016.pdf
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DriversABiologicallyContextualized_2016.pdf.txt