Polychlorinated biphenyls (PCBs) and risk of dementia and Parkinson disease: A population-based cohort study in a North Italian highly polluted area

Raffetti, Elena; Donato, Francesco; Palma, Giuseppe De; Leonardi, Lucia; Sileo, Claudio Vito; Magoni, Michele

doi:10.1016/j.chemosphere.2020.127522

Cited by 20 publications

(7 citation statements)

References 35 publications

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“…Since PCB serum levels have been linked to chronic diseases, their possible association with the incidence of all-cause dementia and Parkinson’s disease was also assessed using a population-based prospective cohort study in a north Italian highly polluted area [ 157 ]. A positive association between the onset of dementia not mediated by hypertension and total PCB serum levels was observed, whereas the unstable risk estimates for Parkinson’s disease did not permit to conclude a possible association.…”

Section: Effects Of Pcbs On Human Healthmentioning

confidence: 99%

“…Among all 209 compounds classified as PCBs, 12 (i.e., PCB 77,81,105,114,118,123,126,156,157,167,169 and 189) have physio-chemical and toxicological properties comparable to those of dioxins and furans and are, therefore, called dioxin-like PCBs. Being all coplanar, they can bind to the aryl hydrocarbon receptor (AhR), which is the canonical receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin [25].…”

Section: Introductionmentioning

confidence: 99%

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Polychlorinated Biphenyls (PCBs) in the Environment: Occupational and Exposure Events, Effects on Human Health and Fertility

Montano

Pironti

Pinto

et al. 2022

Toxics

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In the last decade or so, polychlorinated biphenyls (PCBs) garnered renewed attention in the scientific community due to new evidence pointing at their continued presence in the environment and workplaces and the potential human risks related to their presence. PCBs move from the environment to humans through different routes; the dominant pathway is the ingestion of contaminated foods (fish, seafood and dairy products), followed by inhalation (both indoor and outdoor air), and, to a lesser extent, dust ingestion and dermal contact. Numerous studies reported the environmental and occupational exposure to these pollutants, deriving from building materials (flame-retardants, plasticizers, paints, caulking compounds, sealants, fluorescent light ballasts, etc.) and electrical equipment. The highest PCBs contaminations were detected in e-waste recycling sites, suggesting the need for the implementation of remediation strategies of such polluted areas to safeguard the health of workers and local populations. Furthermore, a significant correlation between PCB exposure and increased blood PCB concentrations was observed in people working in PCB-contaminated workplaces. Several epidemiological studies suggest that environmental and occupational exposure to high concentrations of PCBs is associated with different health outcomes, such as neuropsychological and neurobehavioral deficits, dementia, immune system dysfunctions, cardiovascular diseases and cancer. In addition, recent studies indicate that PCBs bioaccumulation can reduce fertility, with harmful effects on the reproductive system that can be passed to offspring. In the near future, further studies are needed to assess the real effects of PCBs exposure at low concentrations for prolonged exposure in workplaces and specific indoor environments.

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Section: Effects Of Pcbs On Human Healthmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polychlorinated Biphenyls (PCBs) in the Environment: Occupational and Exposure Events, Effects on Human Health and Fertility

Montano

Pironti

Pinto

et al. 2022

Toxics

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“…with PCBs, though correlations in the positive (Raffetti et al, 2020) and the negative (Warembourg et al, 2019) direction have both been found. Increases in systolic and diastolic blood pressure have also been previously associated with high fish intake during pregnancy (Warembourg et al, 2019), which is known to increase exposure to PCBs.…”

Section: Placental Dna Co-methylation Modules Are Correlated With Mat...mentioning

confidence: 94%

Networks of placental DNA methylation correlate with maternal serum PCB concentrations and child neurodevelopment

Mouat

Neier

et al. 2022

Preprint

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Background: Gestational exposure to polychlorinated biphenyls (PCBs) has been associated with elevated risk for neurodevelopmental disorders. The mechanism of risk is unclear but may involve placental epigenetics. Prior studies have associated differential placental DNA methylation with maternal PCB exposure or with increased risk of autism spectrum disorder (ASD). However, sequencing-based placental methylomes have not previously been tested for simultaneous associations with maternal PCB levels and child neurodevelopmental outcomes. Objectives: We aimed to identify placental DNA methylation patterns associated with maternal PCB levels and child neurodevelopmental outcomes in the high-risk ASD MARBLES cohort. Methods: We measured 209 PCB congeners in 104 maternal serum samples collected at delivery. We identified networks of DNA methylation from 147 placenta samples using the Comethyl R package, which performs weighted gene correlation network analysis for whole genome bisulfite sequencing data. We tested placental DNA methylation modules for association with maternal serum PCB levels, child neurodevelopment, and other participant traits. Results: PCBs 153 + 168, 170, 180 + 193, and 187 were detected in over 50% of maternal serum samples and were highly correlated with one another. Consistent with previous findings, maternal age was the strongest predictor of serum PCB levels, alongside year of sample collection, pre-pregnancy BMI, and polyunsaturated fatty acid levels. Twenty seven modules of placental DNA methylation were identified, including five which significantly correlated with one or more PCBs, and four which correlated with child neurodevelopment. Two modules associated with maternal PCB levels as well as child neurodevelopment, and mapped to CSMD1 and AUTS2, genes previously implicated in ASD and identified as differentially methylated regions in mouse brain and placenta following gestational PCB exposure. Conclusions: Placental DNA co-methylation modules were associated with maternal PCBs and child neurodevelopment. Methylation of CSMD1 and AUTS2 could potentially be mechanistically involved in ASD risk following maternal PCB exposure.

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“…In addition, mice that ingested PCBs accumulate the chemical primarily in their hearts, spleens, and large intestines suggesting that exposure through the gastrointestinal route could predispose to a body-first subtype [ 70 ]. Research on PD risk from PCBs has been inconsistent [ 71 ], but their high levels and continued persistence in the food supply raise concerns for their role in body-first Lewy body disorders [ 72–74 ].…”

Section: Body-first Model and Ingested Environmental Toxicantsmentioning

confidence: 99%

The Body, the Brain, the Environment, and Parkinson’s Disease

Dorsey,

De Miranda,

Horsager

et al. 2024

JPD

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The brain- and body-first models of Lewy body disorders predict that aggregated alpha-synuclein pathology usually begins in either the olfactory system or the enteric nervous system. In both scenarios the pathology seems to arise in structures that are closely connected to the outside world. Environmental toxicants, including certain pesticides, industrial chemicals, and air pollution are therefore plausible trigger mechanisms for Parkinson’s disease and dementia with Lewy bodies. Here, we propose that toxicants inhaled through the nose can lead to pathological changes in alpha-synuclein in the olfactory system that subsequently spread and give rise to a brain-first subtype of Lewy body disease. Similarly, ingested toxicants can pass through the gut and cause alpha-synuclein pathology that then extends via parasympathetic and sympathetic pathways to ultimately produce a body-first subtype. The resulting spread can be tracked by the development of symptoms, clinical assessments, in vivo imaging, and ultimately pathological examination. The integration of environmental exposures into the brain-first and body-first models generates testable hypotheses, including on the prevalence of the clinical conditions, their future incidence, imaging patterns, and pathological signatures. The proposed link, though, has limitations and leaves many questions unanswered, such as the role of the skin, the influence of the microbiome, and the effects of ongoing exposures. Despite these limitations, the interaction of exogenous factors with the nose and the gut may explain many of the mysteries of Parkinson’s disease and open the door toward the ultimate goal –prevention.

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Polychlorinated biphenyls (PCBs) and risk of dementia and Parkinson disease: A population-based cohort study in a North Italian highly polluted area

Cited by 20 publications

References 35 publications

Polychlorinated Biphenyls (PCBs) in the Environment: Occupational and Exposure Events, Effects on Human Health and Fertility

Polychlorinated Biphenyls (PCBs) in the Environment: Occupational and Exposure Events, Effects on Human Health and Fertility

Networks of placental DNA methylation correlate with maternal serum PCB concentrations and child neurodevelopment

The Body, the Brain, the Environment, and Parkinson’s Disease

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