Occupational exposure to pesticides increases the risk of incident AD

Hayden, K. M.; Norton, Maria C.; Darcey, Dennis J.; Østbye, Truls; Zandi, Peter P.; Breitner, John C.S.; Welsh‐Bohmer, Kathleen A.

doi:10.1212/wnl.0b013e3181dd4423

Cited by 321 publications

(187 citation statements)

References 25 publications

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“…It is also important to note there is a small but growing body of literature to suggest that OP exposure may even represent a potential risk factor for Alzheimer's disease as well as some of the other neurodegenerative disorders mentioned previously (Hancock et al, 2008;Hayden et al, 2010;Zaganas et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Gao

Naughton

Wulff

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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The extensive use of organophosphates (OPs) is an ongoing environmental health concern due to multiple reports of OPrelated neurologic abnormalities. The mechanism of the acute toxicity of OPs has been attributed to inhibition of acetylcholinesterase (AChE), but there is growing evidence that this may not account for all the long-term neurotoxic effects of OPs. In previous experiments (using ex vivo and in vitro model systems) we observed that the insecticide OP chlorpyrifos impaired the movements of vesicles and mitochondria in axons. Here, using a time-lapse imaging technique, we evaluated the OP-nerve agent diisopropylfluorophosphate (DFP) across a wide range of concentrations (subnanomolar to micromolar) for effects on fast axonal transport of membrane-bound organelles (MBOs) that contain the amyloid precursor protein (APP) tagged with the fluorescent marker Dendra2 (APPDendra2). Both 1 and 24 hours of exposure to DFP and a positive control compound, colchicine, resulted in a decrease in the velocity of anterograde and retrograde movements of MBOs and an increase in the number of stationary MBOs. These effects occurred at picomolar (100 pM) to low nanomolar (0.1 nM) concentrations that were not associated with compromised cell viability or cytoskeletal damage. Moreover, the effects of DFP on axonal transport occurred at concentrations that did not inhibit AChE activity, and they were not blocked by cholinergic receptor antagonists. Given the fundamental importance of axonal transport to neuronal function, these observations may explain some of the long-term neurologic deficits that have been observed in humans who have been exposed to OPs.

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Section: Discussionmentioning

confidence: 99%

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Gao

Naughton

Wulff

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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“…Moreover, several studies have recognized that chronic or occupational pesticide exposure is a possible risk factor for dementia. For example, one of our selected cohort studies 12 reported an increased risk for all-cause dementia among individuals who had been exposed to pesticides (HR = 1.38; 95% CI = 1.09, 1.76). In addition, the Canadian Study of Health and Aging found that exposure to occupational pesticides doubles the risk of vascular dementia 26,27 .…”

Section: Discussionmentioning

confidence: 99%

“…Evidence from in-vitro models and animal studies suggests that long-term/low-dose pesticide exposure may lead to the neuronal loss in specific brain regions, resulting in subsequent cognitive impairment, decreased memory and attention, and loss of motor function 10,11 . These neurobehavioral dysfunctions may ultimately lead to AD and other forms of dementia later in life 12,13 . Pesticides are known neurotoxins.…”

mentioning

confidence: 99%

Effects of Detraining on Ach, AchE, β-amyloid, Apolipoprotein Expression and Cognitive Function in Brain Tissue of Memory Impairment Rats

정¹,

박²,

윤³

2017

Exerc Sci

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Evidence suggests that lifelong cumulative exposure to pesticides may generate lasting toxic effects on the central nervous system and contribute to the development of Alzheimer's disease (AD). A number of reports indicate a potential association between long-term/low-dose pesticide exposure and AD, but the results are inconsistent. Therefore, we conducted a meta-analysis to clarify this association. Relevant studies were identified according to inclusion criteria. Summary odds ratios (ORs) were calculated using fixed-effects models. A total of seven studies were included in our meta-analysis. A positive association was observed between pesticide exposure and AD (OR = 1.34; 95% confidence interval [CI] = 1.08, 1.67; n = 7). The summary ORs with 95% CIs from the crude and adjusted effect size studies were 1.14 (95% CI = 0.94, 1.38; n = 7) and 1.37 (95% CI = 1.09, 1.71; n = 5), respectively. The sensitivity analyses of the present meta-analysis did not substantially modify the association between pesticide exposure and AD. Subgroup analyses revealed that high-quality studies tended to show significant relationships. The present meta-analysis suggested a positive association between pesticide exposure and AD, confirming the hypothesis that pesticide exposure is a risk factor for AD. Further highquality cohort and case-control studies are required to validate a causal relationship.Alzheimer's disease (AD) is the most common progressive neurological disease and results in an irreversible loss of neurons 1 . Late-onset AD, which typically develops after age 60, is the most common form and is characterized by the insidious onset of dementia, progressive memory loss, and cognitive decline ultimately leading to dysfunction in daily life and work abilities 2 . Pathologically, amyloid plaques and neurofibrillary tangles are the main forms of aggregated proteins involved in AD. Amyloid plaques are visible protein aggregates derived from the dimers and oligomers of brain amyloid-β protein, while neurofibrillary tangles are composed of a compact filamentous network of helical filaments of hyperphosphorylated tau protein. Together these neuropathological changes are thought to result in the loss of synapses and neuronal cell death, leading in cognitive dysfunction 3,4 . The aetiology of late-onset AD remains largely unknown but is believed to be multifaceted, resulting from both genetic and environmental factors 5 . The main risk factor is clearly age, though research has identified some genetic risk factors that may account for a small percentage of AD cases 6 . The most well established genetic component of AD risk is the APOE-ε 4 allele 7,8 . Epidemiological studies have reported a higher prevalence of AD in rural areas than in urban settings. Over the past decades, pesticides have been used to increase the productivity and the specialization of cultures in rural areas 9 . Evidence from in-vitro models and animal studies suggests that long-term/low-dose pesticide exposure may lead to the neuronal loss in specific brain regi...

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“…A significant rise in Alzheimers and other forms of dementia through exposure to organochlorine pesticides has been suggested (Hayden et al 2010). A link between thyroid disorders and organochlorine exposure in women in farming communities of Iowa and North Carolina has also been reported (Goldner et al 2010).…”

Section: Long-term Health Effectsmentioning

confidence: 99%

The Trading and Use of Agrochemicals

Hough

2013

Issues in Agroecology – Present Status and Future Prospectus

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Occupational exposure to pesticides increases the risk of incident AD

Abstract: Background: Commonly used organophosphate and organochlorine pesticides inhibit acetylcholines-

Cited by 321 publications

References 25 publications

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

Effects of Detraining on Ach, AchE, β-amyloid, Apolipoprotein Expression and Cognitive Function in Brain Tissue of Memory Impairment Rats

The Trading and Use of Agrochemicals

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