Tuesday, February 4, 2014

Pesticide Exposure Linked to Alzheimer's Disease Risk

By Becca Yeamans

Alzheimer’s disease (AD), a very common neurological disease, has continued to see a growing trend over the past few decades, with projections increasing to up to 3-fold over the next four decades1.  Exactly what causes AD is still unknown, though there are many avenues of research where some progress is being made.  Due to the complexity of the disease, it’s been extremely difficult to find out what it is caused by, let alone a cure.  Studies have found links to AD in genetic, environmental, and lifestyle factors, which you can imagine would complicate the picture greatly with so much variability2.  So far, genetic factors have only been tied to less than half of diagnosed AD cases, leaving a majority of AD cases to be caused by environmental or lifestyle factors.

One earlier study strongly hinted at a connection between AD and pesticide exposure, specifically DDE, a metabolite of the organochlorine pesticide, DDT, showing that serum DDE levels in patients with AD were significantly higher than serum DDE levels of control (no AD) patients, in addition to a significant association between DDE levels and AD diagnosis3

Wishing to confirm (or refute) these findings with a larger sample size, collaborating researchers from Rutgers University, Emory University, and the University of Texas Southwestern Medical Center recently published a study examining the difference between brain and serum DDE levels, and also whether or not DDE or DDT had any effect on amyloid beta expression, the protein that is most commonly associated with AD4.

The results they found were intriguing:  while DDE was found to be present in 70% of control (no AD) patients and 80% of AD patients, serum DDE levels in AD patients were 3.8 times higher than serum DDE levels in control patients.  This is fascinating to note, as it seems while the vast majority of all patients, control or AD, tested positive for the pesticide DDE in their blood, the levels of DDE in those patients with AD were significantly higher than the levels of DDE in patients without the disease.  Additionally, no other pesticides were found in the serum samples of patients other than DDE.

The results of this study also confirmed the presence of the APOE ɛ4 allele in AD patients, which is an allele for a gene known to be associated with AD.  Interestingly, after comparing different genotypes, the association between DDE levels and AD diagnosis did not change, meaning that even if someone did not have the APOE ɛ4 allele, they still had a greater chance of having a diagnosis of AD if their serum DDE levels were high.  This indicates that while the presence of the APOE ɛ4 allele is associated with AD, not all patients with AD will possess the gene, strongly indicating an environmental influence at work.

In terms of cognitive testing, the study found that mental examination scores were significantly lower in those patients with higher levels of serum DDE, while those with lower serum DDE levels fared much better in cognitive tests.  Interestingly, there was a significant interaction between APOE ɛ4 presence and DDE levels in regards to cognitive test scores.  Specifically, those that possessed the APOE ɛ4 allele and that had high levels of serum DDE scored significantly lower on mental/cognitive tests than those without the APOE ɛ4 allele and similar serum DDE levels. 

Finally, it was noted that levels of DDE in the brain were highly correlated with DDE levels in serum, thereby confirming that using measurements of serum DDE is an acceptable substitute for measuring brain DDE levels (good news—since you can’t test brain DDE levels until you’re dead).

So, while APOE ɛ4 and DDE levels independently correlate with AD diagnoses, it appears that having BOTH the APOE ɛ4 allele PLUS high DDE levels results in a much more severe presentation of disease than if the patient possessed just one or the other.  Additionally, confirming that serum DDE levels are comparable to brain DDE levels may allow doctors to perform simple blood tests on a patient to help estimate their risk of developing AD later in life.  Perhaps by testing serum DDE levels in patients during regular doctor’s visits will allow the doctor to make certain lifestyle change recommendations to the patient to minimize DDE exposure and to help combat the risk of developing AD later in life.

Sources & Further Reading:

1.      Brookmeyer, R., Johnson, E., Ziegler-Graham, K., and Arrighi, H.M. 2007. Forecasting the global burden of Alzheimer’s disease. Alzheimer’s & Dementia 3: 186-191.
2.      Pedersen, N.L. 2010. Reaching the limits of genome-wide significance in Alzheimer’s disease. JAMA 303(18). Editorial.
3.      Richardson, J.R., Shalat, S.L., Buckley, B., Winnik, B., O’Suilleabhain, P., Diaz-Arrastia, R, Reisch, J., and German, D.C. 2009. Elevated serum pesticide levels and risk of Parkinson disease. Archives of Neurology 66(7):870-875.

4.      Richardson, J.R., Roy, A., Shalat, S.L., von Stein, R.T., Hossain, M.M., Buckley, B., Gearing, M., Levey, A.I., and German, D.C. 2014. Elevated serum pesticide levels and risk of Alzheimer disease.  JAMA-Neurology: doi.10.1001/jamaneurol.2013.6030.

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