Résumé
AimsPesticide residues have contaminated our environment and nutrition over the last century. Althoughthese compounds are present at very low concentrations their long-term effects on human health is ofconcern. The link between pesticide residues and Alzheimer’s disease is not clear and difficult toestablish. Thus we investigated the impact of this chronic contamination on the pathological markers ofAlzheimer’s disease in a transgenic mouse model.MethodsTransgenic (J20, hAPPSw/Ind) mice were chronically exposed to a cocktail of fungicide residues at 0.1μg/L in their drinking water for 9 months. The dose applied corresponds to the maximal regulatorylimit dose allowed in drinking water. The effects of pesticide residues was assessed on the pathologicalmarkers of the disease. Then, we studied the dynamics of Aβ aggregation in vivo via a longitudinalstudy using 2-photon microscopy.ResultsWe found that a chronic exposure to three fungicide residues exacerbated aggregation, microgliosisand neuronal loss. These fungicides also increased vascular amyloid aggregates reminiscent of cerebralamyloid angiopathy, between 6 and 9 months of treatment. The mechanism of action revealed an over-expression of the levels of the β-secretase cleaving enzyme (BACE1) combined with impairing Aβclearance through neprylisin (NEP).ConclusionsChronic exposure of the J20 mouse model of Alzheimer’s disease to low doses of fungicidesstrengthened the preexisting pathological markers: neuroinflammation, β-amyloid aggregation and APPβ-processing (Lafon PA et al., 2020). We hypothesize prevention strategies towards pesticide long-termexposure may be an alternative to counterbalance the lack of treatment and to slow-down theworldwide Alzheimer’s epidemic.