Although the cause of Alzheimer disease remains unknown, researchers believe genetic, lifestyle, and environmental factors influence a person’s risk of developing the late-onset form of the disease, the disorder’s most common form. Now research appearing today in JAMA Neurology may shed light on a possible environmental risk factor, exposure to a byproduct of the pesticide DDT (dichlorodiphenyltrichloroethane).
The United States made wide use of DDT from the 1940s through the early 1970s in agriculture as a pesticide and for controlling vector-borne diseases in military and civilian populations. Although the US Environmental Protection Agency banned its use in 1972, a DDT metabolite, dichlorodiphenyldichloroethylene (DDE), which has a long half-life (estimated to be between 8 to 10 years), remains in the soil and water. DDT is also still used in some countries, both legally and illegally.
In a case-controlled study, researchers looked for the presence of DDE in existing serum samples from 86 patients with Alzheimer disease and 79 control participants. They found that although DDE was detected in 80% of patients with Alzheimer disease and 70% of control participants, levels of DDE were 3.8-fold higher in those with the disease when compared with control participants. The highest tertile of DDE exposure was associated with a 4.18-fold increased risk for Alzheimer disease compared with the lowest tertile. The researchers also found a genetic association: carriers of a particular variant of the gene encoding apolipoprotein E (APOE 4) appeared to be more susceptible to the effects of DDE.
Lead author, Jason R. Richardson, PhD, of the Rutgers Robert Wood Johnson Medical School and Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey, talks with news@JAMA about his team’s findings.
news@JAMA: How did you happen to consider DDE as something to study for Alzheimer disease risk?
Dr Richardson: In 2009 we published a study in the then Archives of Neurology looking at pesticide chemicals and Parkinson disease. While we were doing that, we had a control group but thought to add another neurodegenerative disease. So we took 20 samples from patients with Alzheimer disease and we found higher levels of DDE in the Alzheimer’s samples. It was intriguing, but you don’t want to get too excited about 20 samples. So we cobbled together some funds and now we’ve confirmed that original sample.
news@JAMA: So what comes next?
Dr Richardson: Our data calls for more research to find out why this association occurs. I hope our colleagues in the scientific community, with a much larger cohort, can replicate our findings.
news@JAMA: If your findings are confirmed and added to, what are the potential clinical implications?
Dr Richardson: Early detection and treatment is important for neurodegenerative disease, so if you can identify those at higher risk and get them to the clinic earlier maybe your intervention will be more successful.
news@JAMA: It seems a lot of us have DDE circulating in our bodies. Why?
Dr Richardson: We have legacy contamination in the United States and DDE has a long half-life. So especially meat, fish, and diary can harbor these types of chemicals.
news@JAMA: Does it surprise you that the World Health Organization has called for the reintroduction of DDT for malaria eradication while the research community continues to caution about a potential association with neurodegenerative diseases?
Dr Richardson: From a medical standpoint, DDT was an amazing insecticide. Where used, it eradicated malaria, so this is not a black and white issue. I asked my medical school students to determine as best they could whether DDT should be reintroduced. They looked at all the evidence and said it should be brought back to eradicate malaria in the developing world, but you need to be cognizant to reduce exposure as much as you can. They determined the benefits outweigh the risk.