Jason R. Richardson, Ph.D., Richard T. von Stein, Ph.D.
Robert Wood Johnson Medical School, Rutgers University
NIEHS Grants P30ES005022, T32ES007148, R01ES015991
In one of the first studies to identify a strong environmental risk factor for Alzheimer's disease, NIEHS grantees report that patients with Alzheimer's have significantly higher levels of a dichlorodiphenyltrichloroethane (DDT) metabolite than people without the disease. Researchers also found evidence of a gene-environment interaction, as well as a possible mechanism for the pesticide’s effects.
In the United States, DDT was used extensively as an insecticide from the 1940s through 1972. It persists in the environment today and is still used to control malaria in some countries. DDE, a DDT metabolite, accumulates in tissues as people grow older.
The study compared 86 Alzheimer's patients from Alzheimer’s centers in Georgia and Texas and 79 healthy elderly controls. The researchers first examined DDE levels, finding that they were 3.8-fold higher in the serum of patients with Alzheimer’s disease compared to control participants. DDE levels in the highest third of the range studied were associated with an odds ratio of 4.18 for increased Alzheimer’s disease risk and lower scores for the Mini-Mental State Examination, which is used to screen for cognitive impairment.
The researchers also looked at the role of the apolipoprotein E (APOE) genotype. They divided the study participants into three groups based on their DDE levels and found that participants in the group with the highest DDE levels who carried the APOE ε4 allele had Mini-Mental State Examination scores 1.753 points lower than those in the same group who carried the APOE ε3 allele. This finding provides evidence that carriers of an APOE4 ε4 allele may be more susceptible to the effects of DDE. The researchers also exposed cultured neuronal cells to DDT or DDE at levels observed in highly exposed people in the United States and observed an increase in amyloid precursor protein, which is linked with Alzheimer’s disease. This points to a possible mechanism for the association between DDT exposure and Alzheimer’s disease.
Citation: Richardson JR, Roy A, Shalat SL, von Stein RT, Hossain MM, Buckley B, Gearing M, Levey AI, German DC. 2014. Elevated serum pesticide levels and risk for Alzheimer disease. 2014. JAMA Neurol. 71(3):284-290.