Past exposure to the banned pesticide DDT is "strikingly" linked to the development of Alzheimer's in later life, a study has shown.
People with the highest levels of DDT residue in their blood were four times more likely than average to succumb to the devastating disease, scientists found.
While experts urged caution over the results, laboratory tests have identified a plausible way that pesticide chemicals might trigger Alzheimer's-related changes in the brain.
Exposure to high concentrations of DDT, or its long-lasting derivative DDE, raises levels of a protein in nerve cells associated with a key hallmark of the disease.
In the patient study, the US team looked for DDE - produced when DDT breaks down in the body - in the blood of 86 Alzheimer's patients and 79 healthy volunteers with an average age of 74.
DDE levels were almost four times higher in the Alzheimer's patients - and those in the highest third of the exposure range assessed in the study quadrupled the chances of developing the disease.
"This is one of the first studies identifying a strong environmental risk factor for Alzheimer's disease," said Dr Allan Levey, director of the Alzheimer's Disease Research Center at Emory University School of Medicine in Atlanta, who co-led the study.
"The magnitude of the effect is strikingly large - it is comparable in size to the most common genetic risk factor for late-onset Alzheimer's."
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DDT has been banned in the US since 1972 and in the UK since the 1980s as a result of work showing that the pesticide is harmful to wildlife and the environment.
Yet there are fears that its long-lasting effects live on in people exposed to the chemical when it was widely used to keep food crops free of insect pests.
DDT has a very long "half life" - the length of time it takes to reduce to half its original level - in the body of between eight to 10 years.
Levels of its DDE metabolite accumulate in body tissues as people age, the researchers point out. They believe this could be one reason why age is by far the largest risk factor for Alzheimer's disease.
In addition, DDT may continue to contaminate food products imported from countries where its use is still permitted to control malaria-spreading mosquitoes.
"We are still being exposed to these chemicals.. both because we get food products from other countries and because DDE persists in the environment for a long time," said Dr Jason Richardson, from Rutgers University in New Jersey, who led the research published in the journal JAMA Neurology.
Studies of cultured brain cells have shown that exposure to DDT and DDE raises levels of a precursor to beta-amyloid, a protein that forms sticky clumps in the brains of Alzheimer's patients.
Beta-amyloid plaques increase in the brain as the disease progresses and are thought to play a key role in Alzheimer's.
The new research suggests that exposure to DDT may directly contribute to beta-amyloid plaque development, according to Dr Richardson.
However, the scientists stress that not everyone exposed to DDT will develop Alzheimer's. Some Alzheimer's patients in the study had no trace of the chemical in their blood, and some healthy participants showed evidence of high exposure.
One deciding factor could be the presence or absence of a mutant gene called ApoE, known to be strongly linked to Alzheimer's.
Genetic risk factors such as ApoE may combine with environmental factors such as exposure to pesticides to drive the disease forward, say the scientists.
Dr Simon Ridley, from the charity Alzheimer's Research UK, said: "It's important to note that this research relates to DDT, a pesticide that has not been used in the UK since the 1980s.
"While this small study suggests a possible connection between DDT exposure and Alzheimer's, we don't know whether other factors may account for these results. We can't conclude from these findings that pesticide exposure causes Alzheimer's, and much more research would be needed to confirm whether this particular pesticide may contribute to the disease.
"Research to understand the possible environmental risk factors for Alzheimer's can help us make informed decisions to reduce these risks."
Carol Brayne, professor of public health medicine at Cambridge University, said it was too early to come to any conclusions about a possible link between DDT exposure and Alzheimer's.
"I would be very, very cautious indeed about over-interpreting the results at this stage without confirmation from research based on stronger designs," he added.
But he said the research had produced a "very interesting result" that should be followed up by further studies.
DDT, or dichlorodiphenyltrichloroethane, was developed during the Second World War and used extensively in agriculture from the 1940s onwards.
Its agricultural use was banned worldwide in 2001 under the Stockholm Convention on Persistent Organic Pollutants. The Convention included an exemption that permitted its continued use in combating malaria.
Prof Alan Boobis, an expert in biochemical pharmacology at Imperial College London, said: "The authors of the paper have looked for associations between DDT/DDE levels and Alzheimer's disease occurrence, but from the evidence they present we still don't know whether DDT/DDE might be associated with Alzheimer's disease through the much higher exposures that occurred several decades ago, or through the lower levels of exposure occurring now from residual environmental levels.
"This distinction is important because some confounding factors have not been accounted for in this study, for example co-exposures in the past, many of which would no longer be detectable in biological samples."
David Coggon, professor of occupational and environmental medicine at the University of Southampton, said: "The findings should be a stimulus to further research using more rigorous epidemiological methods, but of themselves, they do not provide strong evidence of a hazard.
"As DDT has been banned in the UK for many years, there is no scope for additional regulatory controls on a precautionary basis."
Dr Doug Brown, director of research at the Alzheimer's Society, said: "Many of us recall the controversial pesticide DDT, which was banned in the UK following concerns about its affect on wildlife and humans. This small study suggests that increased levels of DDT in the blood might be linked to an increased risk of Alzheimer's disease.
'Whilst this isn't the first time DDT has been linked to health problems, it is hard to draw any firm conclusions from this small sample of people from the United States. Alzheimer's disease is a complex condition and we know that genetics, the environment and lifestyle factors can all contribute to its development. More research is needed to unravel its causes and determine whether testing for pesticides in the blood could be useful to predict who is at greater risk."