Medscape... JAMA Neurol. 2014;71:284-290 Study Summary Various genetic, environmental, and lifestyle factors may contribute to the etiology of late-onset Alzheimer disease (AD), but these factors have not been completely elucidated. Occupational pesticide exposures may be linked to AD, on the basis of limited epidemiologic evidence. Richardson and colleagues previously described[1] 20 patients with AD and elevated serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT).
The goal of the current case/control study was to examine the association between serum levels of DDE and AD and to identify any modulating effect on this association of apolipoprotein E (APOE) genotype. Patients with AD (n = 86) and controls (n = 79) from the Emory University Alzheimer's Disease Research Center and the University of Texas Southwestern Medical School's Alzheimer's Disease Center underwent testing of serum DDE levels.
Compared with control participants, AD cases had 3.8-fold higher serum levels of DDE (mean, 2.64 ± 0.35 ng/mg cholesterol vs 0.69 ± 0.1 ng/mg cholesterol; P < .001). DDE serum levels were highly correlated with DDE brain levels (Spearman rho = 0.95). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% confidence interval, 2.54-5.82; P < .001), as well as with lower Mini-Mental State Examination scores (-1.605; range, -3.095 to -0.114; P < .0001).
In the highest tertile of DDE serum levels, Mini-Mental State Examination scores were -1.753 points lower among participants with an APOE epsilon 4 allele than among those with an APOE epsilon 3 allele (P interaction = .04). Exposing human neuroblastoma cells to DDT or DDE resulted in higher levels of amyloid precursor protein. Viewpoint
The findings of this small case/control study suggest an association of elevated serum DDE levels with increased AD risk, particularly among carriers of an APOE4 epsilon 4 allele. This association is biologically plausible, because exposure of human neuroblastoma cells to DDT and DDE was associated with increased amyloid precursor protein levels. Identifying carriers of an APOE epsilon 4 allele who have elevated DDE serum levels may allow early identification of preclinical AD at a time when early intervention could be most effective