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Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases.

ABSTRACT: Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (A?) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as ?-synuclein (?-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase A?, P-Tau, ?-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of A? and ?-syn, and the reduced activity/protein levels of A? degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.

SUBMITTER: Chin-Chan M

PROVIDER: S-EPMC4392704 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases.

Chin-Chan Miguel M Navarro-Yepes Juliana J Quintanilla-Vega Betzabet B

Frontiers in cellular neuroscience 20150410

Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cad ...[more]

PMID: 25914621

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Project description:ImportancePosttraumatic stress disorder (PTSD) has been associated with increased risk for dementia. Less is known, however, about other stress-related disorders and their associations with neurodegenerative diseases.ObjectiveTo examine the association between stress-related disorders and risk for neurodegenerative diseases.Design, setting, and participantsThis population-matched and sibling cohort study was conducted in Sweden using data from nationwide health registers, including the Swedish National Patient Register. Individuals who received their first diagnosis of stress-related disorders between January 1, 1987, and December 31, 2008, were identified. Individuals who had a history of neurodegenerative diseases, had conflicting or missing information, had no data on family links, or were aged 40 years or younger at the end of the study were excluded. Individuals with stress-related disorders were compared with the general population in a matched cohort design; they were also compared with their siblings in a sibling cohort. Follow-up commenced from the age of 40 years or 5 years after the diagnosis of stress-related disorders, whichever came later, until the first diagnosis of a neurodegenerative disease, death, emigration, or the end of follow-up (December 31, 2013), whichever occurred first. Data analyses were performed from November 2018 to April 2019.ExposuresDiagnosis of stress-related disorders (PTSD, acute stress reaction, adjustment disorder, and other stress reactions).Main outcomes and measurementsNeurodegenerative diseases were identified through the National Patient Register and classified as primary or vascular. Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis were evaluated separately. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% CIs after controlling for multiple confounders.ResultsThe population-matched cohort included 61?748 exposed individuals and 595?335 matched unexposed individuals. A total of 44?839 exposed individuals and their 78?482 unaffected full siblings were included in the sibling cohort analysis. The median (interquartile range) age at the start of follow-up was 47 (41-56) years, and 24 323 (39.4%) of the exposed individuals were male. The median (interquartile range) follow-up was 4.7 (2.1-9.8) years. Compared with unexposed individuals, individuals with a stress-related disorder were at an increased risk of neurodegenerative diseases (HR, 1.57; 95% CI, 1.43-1.73). The risk increase was greater for vascular neurodegenerative diseases (HR, 1.80; 95% CI, 1.40-2.31) than for primary neurodegenerative diseases (HR, 1.31; 95% CI, 1.15-1.48). A statistically significant association was found for Alzheimer disease (HR, 1.36; 95% CI, 1.12-1.67) but not Parkinson disease (HR, 1.20; 95% CI, 0.98-1.47) or amyotrophic lateral sclerosis (HR, 1.20; 95% CI, 0.74-1.96). Results from the sibling cohort corroborated results from the population-matched cohort.Conclusions and relevanceThis study showed an association between stress-related disorders and an increased risk of neurodegenerative diseases. The relative strength of this association for vascular neurodegenerative diseases suggests a potential cerebrovascular pathway.

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Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases.

Publications

Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases.

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