Title | Drivers: A Biologically Contextualized, Cross-Inferential View of the Epidemiology of Neurodegenerative Disorders. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | de Pedro-Cuesta, J, Martínez-Martín, P, Rábano, A, Alcalde-Cabero, E, López, FJosé Garc, Almazán-Isla, J, Ruiz-Tovar, M, Medrano, M-J, Avellanal, F, Calero, O, Calero, M |
Journal | J Alzheimers Dis |
Volume | 51 |
Issue | 4 |
Pagination | 1003-22 |
Date Published | 2016 |
ISSN | 1875-8908 |
Keywords | Age Factors, Aging, Amyloid Precursor Protein Secretases, Apolipoproteins E, Aspartic Acid Endopeptidases, Creutzfeldt-Jakob Syndrome, Environment, Female, Humans, Incidence, Male, Neurodegenerative Diseases, Personality, Risk Factors, Vascular Diseases |
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. 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. |
DOI | 10.3233/JAD-150884 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 26923014 |
PubMed Central ID | PMC4927850 |