Drivers: A Biologically Contextualized, Cross-Inferential View of the Epidemiology of Neurodegenerative Disorders.
J Alzheimers Dis
; 51(4): 1003-22, 2016.
Article
en En
| MEDLINE
| ID: mdl-26923014
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-ß, tau, or α-synuclein, acting across entities. OBJECTIVES ANDMETHODS:
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, APOEÉ4, 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-ß, tau, Langerhans islet peptide, and transthyretin) or established combinations of these.Palabras clave
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Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Vasculares
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Envejecimiento
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Enfermedades Neurodegenerativas
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Ambiente
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Año:
2016
Tipo del documento:
Article