Exposure to the pesticide dichlorodiphenyltrichloroethane (DDT) may heighten the risk of developing Alzheimer’s disease, according to a small study published in the January 27 JAMA Neurology online. Researchers led by Jason Richardson at Rutgers-Robert Wood Johnson Medical School, Piscataway, New Jersey, found that older adults with high levels of a DDT metabolite in their blood were four times more likely to have AD than were those with low levels. This resembles the risk conferred by an ApoE4 allele, the main genetic risk factor for sporadic AD. Moreover, the authors report that adding DDT to a neuronal cell line ramped up amyloid precursor protein levels, hinting that the chemical might directly contribute to pathogenesis. If these findings are confirmed by larger studies, they could have implications for the use of DDT worldwide. Though the chemical has been banned in the United States since 1972, many countries still use it, and the World Health Organization recommends it to combat malaria (see Rehwagen, 2006).
Other researchers expressed enthusiasm for the paper and said follow-up studies should be done. “I think it’s very impressive. The strength of the finding was shocking,” said Sid O’Bryant at the University of North Texas Health Science Center, Fort Worth. However, commentators cautioned that these data should be considered preliminary, and that the implications for public health are not yet clear. “For now, this is not something the general public needs to worry about. The findings will need to be replicated and if they are, we still need to determine the level of exposure that is related to increased risk of AD,” Kathleen Hayden at Duke University, Durham, North Carolina, wrote to Alzforum.
A handful of prior studies have hinted that various chemicals, such as air pollutants, lead, and pesticides, increase the risk of cognitive decline or AD (see Feb 2005 news story; Feb 2012 news story; Hayden et al., 2010; Singh et al., 2012). The evidence is stronger for a link between pesticides and Parkinson’s disease (see Nov 2000 news story; Baldi et al., 2003; Tanner et al., 2011; Chhillar et al., 2013). Richardson and colleagues previously found that high serum levels of an organochlorine pesticide, β-hexachlorocyclohexane, quadruple the chances of getting PD (see Richardson et al., 2009; Richardson et al., 2011). That study included 20 Alzheimer’s patients as controls. In these patients, the authors noticed high serum levels of the DDT metabolite p,p’-dichlorodiphenyldichloroethylene (DDE), making them wonder if this chemical might predispose people to AD.
To follow up on these results, Richardson and colleagues examined a panel of 16 organochlorines in serum samples from 86 AD patients and 79 age-matched controls seen at Alzheimer’s Disease Research Centers at the University of Texas Southwestern Medical Center, Dallas, and Emory University, Atlanta. The majority of patients and controls had DDE in their blood, but patients had an average of four times as much (see image below), and the researchers calculated that those in the highest tertile had a fourfold increased risk of AD. In addition, AD patients with elevated DDE scored significantly worse on the Mini-Mental State Examination than those with low DDE. (Below, average serum levels of DDE are higher in AD patients than controls. Courtesy of JAMA Neurology, January 27, © 2014 American Medical Association, all rights reserved.)
To see if serum DDE reflected the amount in the brain, the authors examined 11 matched brain and serum samples from the Washington University Alzheimer’s Disease Research Center in St. Louis. Quantities of the chemical corresponded closely, they report. They also wondered if the association between DDT and Alzheimer’s might have a biological basis. After exposing a neuronal cell line to 1μM DDE or DDT for two days, they saw a 50 percent jump in amyloid precursor protein, making such a connection plausible. The 1μM concentration compares to serum levels found in people living near DDT dumping sites (see Kreiss et al., 1981; Gaffney et al., 2005).
However, much more work remains to be done to nail down a link between DDT and AD, Richardson told Alzforum. He plans to repeat the study in an independent group of at least 500 cases and 500 controls, as well as analyzing cohorts drawn from the community instead of Alzheimer’s centers. He will also look more closely at how genetics might modify susceptibility to DDT. Richardson pointed out that some healthy people in his study had very high DDE, which implies that some people have protective factors.
If the results are confirmed, what would that mean for public health? Richardson noted that the serum DDE levels measured in his study resemble those in the general U.S. population, as reported by the Centers for Disease Control and Prevention. About 5 percent of the population has levels on a par with the highest group in this study, he said.
Why does the chemical persist more than 40 years after it was banned? DDT still contaminates soil and water, and people continue to be exposed through their diet, Richardson noted. Also, DDE has a half-life on the order of 10 years, allowing it to linger in the body. Younger people tend to have less of the chemical in their blood, but some minority groups, such as Mexican-Americans and African-Americans, carry high levels even at young ages, Richardson said. The reasons are not clear, but may have to do with diet, occupational exposures, or where people live. In countries such as India and Spain, where DDT is still used, exposures are much higher (see Botella et al., 2004; Bhatnagar et al., 2004). There is no evidence of more AD cases in those countries, however.
DDT remains one of the cheapest and most effective ways to fight malaria, which kills about half a million people each year. “The World Health Organization has judged that the ratio of benefits to risks is probably high enough to keep using DDT for very specific purposes,” said Jennifer Weuve at Rush University, Chicago. Future research might look for ways to ameliorate the effects of DDT exposure, commentators said. For example, O’Bryant noted that some previous research suggests that DDE can be removed from the body by ingesting mineral oil (see Rozman et al., 1983).
Researcher agreed that the issue deserves further study. A first step would be for AD research groups to measure DDE levels in their banked serum and brain samples. Prospective studies could clarify whether DDE exposure jacks up the risk of developing dementia. In an accompanying commentary, Steven DeKosky at the University of Virginia, Charlottesville, and Sam Gandy at Mount Sinai Alzheimer’s Disease Research Center, New York City, wrote, “Identification of the important environmental influences that modulate AD risk represents the next great frontier for discovery … Richardson and colleagues have provided both a wake-up call to explore environmental influences and pointed us to a first area to assess—pesticides.”—Madolyn Bowman Rogers.
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