A metabolite of the pesticide DDT – banned in the United States since 1972 – was associated with late-onset Alzheimer’s disease in a small, case-control study.
Levels of the chemical dichlorodiphenyldichloroethylene (DDE) were nearly four times higher in the serum of Alzheimer’s disease patients than in controls. That translated to almost fourfold higher odds of developing the disease, Jason R. Richardson, Ph.D., of Robert Wood Johnson Medical School, Piscataway, N.J., and his colleagues reported (JAMA Neurol. 2014 Jan. 27 [doi:10.1001/jamaneurol.2013.6030]).
Dr. Jason Richardson
The level of the chemical also showed a strong interaction with the high-risk apolipoprotein E (apo E) epsilon-4 allele in influencing Mini-Mental State Examination (MMSE) scores, wrote Dr. Richardson and his coauthors.
"This suggests that exposure to [the chemical] may contribute to Alzheimer’s disease only in a subset of cases, perhaps those with genetic polymorphisms that render them more susceptible to DDT/DDE exposure."
In 2009, the team reported a significant increase in the risk of Alzheimer’s corresponding with increased levels of DDE in a small cohort of 20 Alzheimer’s patients, compared with controls (Arch. Neurol. 2009;66:870-5 [doi:10.1001/archneurol.2009.89]).
That finding prompted this larger study, which comprised 86 Alzheimer’s patients and 79 control participants from two centers, all of whom provided blood serum for testing. A subset of 11 patient samples also provided brain tissue.
DDE, which concentrates in fat, was found in 70% of controls and 80% of cases. But the mean serum level was 3.8 times higher in cases than in controls (2.64 vs. 0.69 ng/mg cholesterol).
The authors divided the group into tertiles according to DDE level. They performed a multivariate regression that controlled for age, sex, race/ethnicity, and location. Compared with those with the lowest DDE level, those with the highest had significantly higher odds of Alzheimer’s (odds ratio, 4.18). MMSE scores were also significantly lower in the highest tertile than in the lowest.
The presence of an apo E–epsilon-4 allele alone nearly quadrupled the odds of an Alzheimer’s diagnosis (OR, 3.70), and when researchers adjusted for the risk marker, it did not change the association between DDE and Alzheimer’s.
However, MMSE scores were the worst in apo E–epsilon-4 carriers who also had the highest DDE levels. Since DDE levels didn’t differ by genotype, "this is a functional interaction," the investigators concluded.
In matched serum and brain tissue samples from 11 Alzheimer’s patients, DDE levels were similar in both brain and serum. In a separate experiment with cultured neurons, exposure of the cells to DDE or DDT for 48 hours increased levels of amyloid precursor protein by nearly 50%. (Genetic overexpression of amyloid precursor protein is a known risk factor for Alzheimer’s disease.)
Although levels of DDT and DDE have declined significantly over the past 3 decades in the United States, both it and DDE are still found in up to 80% of serum samples in the United States, Dr. Richardson and his team noted. "This is likely the result of the exceptionally long half-life of DDE (approximately 8-10 years) and continuing exposure from the import of food from countries where DDT is still used or from legacy contamination of soil and waterways in the United States. ... Serum concentrations of DDE are much higher elsewhere in the world, where DDT was phased out later or is still used, such as Spain and India."
The study was funded by the National Institutes of Health. None of the authors had any financial disclosures.
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