JAMA Neurol. Published online January 27, 2014. doi:10.1001/jamaneurol.2013.6030
Jason R. Richardson, PhD1,2; Ananya Roy, ScD2; Stuart L. Shalat, ScD1,2; Richard T. von Stein, PhD2; Muhammad M. Hossain, PhD1,2; Brian Buckley, PhD2; Marla Gearing, PhD4; Allan I. Levey, MD, PhD3; Dwight C. German, PhD5
Importance The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20).
Objective To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association.
Design, Setting, and Participants A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer’s Disease Research Center and the University of Texas Southwestern Medical School’s Alzheimer’s Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases.
Main Outcomes and Measures Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status.
Results Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54-5.82; P < .001) and lower Mini-Mental State Examination scores (−1.605; range, −3.095 to −0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were −1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein.
Conclusions and Relevance Elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 ε4 allele may be more susceptible to the effects of DDE. Both DDT and DDE increase amyloid precursor protein levels, providing mechanistic plausibility for the association of DDE exposure with AD. Identifying people who have elevated levels of DDE and carry an APOE ε4 allele may lead to early identification of some cases of AD.
Pesticide DDT Linked to Alzheimer's Disease comment on the above study
- In a previous study of 20 patients with Alzheimer's disease, Richardson and colleagues found that the patients had significantly higher levels of DDE in their blood compared to people without the disease.
- In the new study, the researchers analyzed blood samples from 86 patients with Alzheimer's disease (including the original 20 patients), and 79 people without the disease. Researchers divided the participants into three groups based on their DDE levels.
- The odds of having Alzheimer's disease were about four times greater for those in the group with the highest DDE levels, as compared with the group with the lowest DDE levels.
- Richardson said that if there were a single environmental factor that caused Alzheimer's disease, it would have likely been found by now. Instead, researchers need to study how the environment can interact with the genes of an individual, Richardson said.
Arch Neurol. 2009 Jul;66(7):870-5. doi: 10.1001/archneurol.2009.89.
Richardson JR, Shalat SL, Buckley B, Winnik B, O'Suilleabhain P, Diaz-Arrastia R, Reisch J, German DC.
BACKGROUND: Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains.
OBJECTIVE: To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD.
DESIGN: Case-control study.
SETTING: An academic medical center.
PARTICIPANTS: Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease.
MAIN OUTCOME MEASURES: Levels of 16 organochlorine pesticides in serum samples.
RESULTS: beta-Hexachlorocyclohexane (beta-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of beta-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of beta-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67-11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum beta-HCH and PD.
CONCLUSIONS: These data suggest that beta-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of beta-HCH as a etiologic agent for some cases of PD.
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