Early Environmental Origins of Neurodegenerative Disease in Later Life

Center for Children's Health and the Environment, Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Environmental Health Perspectives (Impact Factor: 7.98). 10/2005; 113(9):1230-3. DOI: 10.1289/ehp.7571
Source: PubMed


Parkinson disease (PD) and Alzheimer disease (AD), the two most common neurodegenerative disorders in American adults, are of purely genetic origin in a minority of cases and appear in most instances to arise through interactions among genetic and environmental factors. In this article we hypothesize that environmental exposures in early life may be of particular etiologic importance and review evidence for the early environmental origins of neurodegeneration. For PD the first recognized environmental cause, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), was identified in epidemiologic studies of drug abusers. Chemicals experimentally linked to PD include the insecticide rotenone and the herbicides paraquat and maneb; interaction has been observed between paraquat and maneb. In epidemiologic studies, manganese has been linked to parkinsonism. In dementia, lead is associated with increased risk in chronically exposed workers. Exposures of children in early life to lead, polychlorinated biphenyls, and methylmercury have been followed by persistent decrements in intelligence that may presage dementia. To discover new environmental causes of AD and PD, and to characterize relevant gene-environment interactions, we recommend that a large, prospective genetic and epidemiologic study be undertaken that will follow thousands of children from conception (or before) to old age. Additional approaches to etiologic discovery include establishing incidence registries for AD and PD, conducting targeted investigations in high-risk populations, and improving testing of the potential neurologic toxicity of chemicals.

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Available from: Leonardo Trasande
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    • "Early-life exposure to certain natural and synthetic chemicals may increase the risk of 41 neurodegenerative and other diseases later in life (Spencer, 1987; Landrigan et al., 2005; 42 Kisby and Spencer, 2011; Fox et al., 2012). The increase in childhood pathologies, such as 43 hyperactivity or memory alterations, and the occurrence of neurodegenerative diseases such 44 as Alzheimer's and Parkinson's diseases in the elderly, may be due in part to the early chronic 45 exposure of pollutants and their related impacts in early stages of life (Corrigan et al., 2000; 46 Bihaqi et al., 2011, 2013, 2014a; Medehouenou et al., 2011, 2014; Jurewicz et al., 2013; 47 Grandjean and Landrigan, 2014). "
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    • "We tested the viability of control (e.g. subject CA) versus patient SM derived neuroprogenitors by MTT assay after 48 hour exposure to Mn, Cu, Cd, and MeHg, all of which have been implicated in PD-relevant neurodegenerative processes and/or as PD environmental risk factors (Buzanska et al., 2009; Gorell et al., 1999; Götz et al., 2002; Jomova et al., 2010; Landrigan et al., 2005; Rivera-Mancía et al., 2010; Squitti et al., 2009; Weiss et al., 2002; Willis et al., 2010; Xu et al., 2011). To control for cell line dependent variability , we used multiple clonal hiPSC lines (lines CA4 and CA6 for subject CA; lines SM3, SM4, and SM5 for subject SM). "
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