Identifying people who have elevated levels of dichlorodiphenyldichloroethylene (DDE), the byproduct of the pesticide dichlorodiphenyltrichloroethane (DDT), and carry an apolipoprotein ε4 (APOε4) allele may lead to early identification of some cases of Alzheimer disease (AD), according to a study published online by JAMA Neurology on Jan. 27.
Numerous factors contribute to a person’s risk of developing AD, including sole possession of the APOε4 allele. Lead author Jason R. Richardson, PhD, of the Rutgers Robert Wood Johnson Medical School and Environmental and Occupational Sciences Institute of Piscataway, New Jersey, and colleagues wrote, “To our knowledge, few studies have explored the potential of environmental exposures to contribute to AD, but occupational exposure to metals, solvents, and pesticide is reported to be a potential environmental contributor.”
Building upon a previous study, Richardson and colleagues evaluated the associations between serum DDE levels, AD, and Mini-Mental State Examination (MMSE) scores in a larger number of cases and control participants from two geographical sites. The researchers additionally examined differential susceptibility by APOε4 genotype status, the relationship between brain and serum levels of DDE, and whether DDT or DDE alters the expression of the amyloid precursor protein (APP) in cultured neuronal cells.
Blood samples from 86 AD patients and 79 controls were utilized in the study. Results revealed that at least one APOε4 allele was found in 35 percent of the control and 65 percent of AD cases. The study’s authors detected DDE in 70 percent of control and 80 percent of AD cases. Mean levels were 3.8-fold higher in the serum of AD cases than those of the control participants.
Scores from the MMSE were significantly lower in the highest DDE tertile. The MMSE score in those with the ε4 allele and DDE levels in the third tertile was significantly lower than those without an ε4 allele. Exposure of human neuroblastoma cells to DDT or DDE increased levels of APP by almost 50 percent.
“Because elevated DDE levels were associated with significantly worse MMSE performance and exacerbated by the presence of an APOE ε4 allele, measurement of serum DDE levels accompanied by APOE genotyping might be a useful clinical measure to identify individuals who may be at risk for AD,” wrote Richardson and colleagues.
While the study benefited from its large sample size and use of sensitivity analysis, limitations remained. Other nonpersistent pesticides could contribute to the development of AD and exposure to DDE may contribute to AD only in a subset of cases.