Immune response cytokines as potential biomarkers for DDT induced neurodegeneration

Rocz Panstw Zakl Hig. 2017;68(2):199-205.

Abstract

Background: The world incidence rate of Alzheimer’s Disease (AD) is 64 cases per 1,000 individuals. Due to the aging population, the prevalence of AD is however increasing and yet, little remains known about the etiology of AD.

Objective: Previous studies suggested relationships between AD, neuro-inflammation and organochloride pesticide exposures, therefore, we aimed to study the association between DDT and possible biomarkers of AD.

Materials and methods: We explored literature on inflammation, pesticide exposure and biomarkers associated with AD. We measured eligible markers in adult C57BL/6J mice treated with DDT for 4 months (dose=3 mg/kg/day); Hippocampi tissue gene expression was quantified by qPCR. IL-1β expression was compared in test vs. control mice using t-tests. Furthermore, we studied population data to: explore the immunological markers, identify gaps and possible approaches for addressing them.

Results: Average serum levels of IL-1β were significantly higher (p<0.05) in the DDT treated mice compared to controls. IL-1β stimulates APP and Aβ41 syntheses, which may be associated with AD pathogenesis. Gaps identified included: (1) Parallel analysis of genetic and environmental risk factors; (2) Definition of toxin-induced neuro-inflammation focusing on microglial physiology. Studies focusing on the physiological effects of DDT, focusing on epigenetic aberrations may aid in the description of the effect of DDT on gene expression; (3) The blood-brain-barrier limits comparisons between peripheral and brain-localized IL-1β and DDT concentrations, suggesting the need for robust measurement schemes. We report that there is still much uncertainty regarding biomarkers associated with AD pathogenesis.

Conclusions: Currently, we cannot confidently report that DDT has a causal role in AD incidence. However, by first quantifying the cytokine concentrations post-exposure to DDT, by measuring the metabolite DDE, we can further explore potential drifts in immune marker concentrations that could provide a platform for future studies.

Publication types

  • Retracted Publication