Regarding pesticides, occupational exposure of farmers to organophosphates has been associated with an increased risk to develop Alzheimer’s disease ( Hayden et al. In vitro treatment with aluminum ( 50 μ M ) on rat cortical neurons revealed A β peptides conformational changes and enhanced aggregation ( Kawahara et al. Moreover, rats orally treated with aluminum ( 20 g / d, twice a week) through diet, from 6 months of age until the end of their life and who developed cognitive deficits, presented an up-regulation of the APP gene and a greater APP accumulation in hippocampal and cortical neurons compared with cognitively intact control rats ( Walton and Wang 2009). Mercury was shown to be involved in the disruption of A β peptide clearance pathways both in vivo and in vitro. Furthermore, an acute injection of lead in a mouse model of Alzheimer’s disease (APP V717F) has resulted in a lower expression of LRP1 in the choroid plexus than injection of vehicle ( Gu et al. However, experimental studies have showed that incubation of SH-SY5Y cells with lead (5 to 100 μ M ) can induce an increase of APP expression and A β peptides secretion, associated with a decreased NEP expression ( Chin-Chan et al. This suggests a potential role of heavy metals in Alzheimer’s disease, but it is not yet clear whether they interfere in the development or the progression of the disease. Human epidemiological studies have showed that circulating levels of certain heavy metals are higher in patients with Alzheimer’s disease than in control patients ( Fathabadi et al. Our hypothesis is that environmental pollutants may corrupt APP metabolism or the A β aggregation process, which may lead to the onset or aggravation of Alzheimer’s disease. The causes leading to these deregulations have not yet been clearly identified.
2014) involved in the A β clearance pathways are major events reinforcing the disease. 2007), and/or receptors such as the low-density lipoprotein receptor-related protein 1 (LRP1) ( Kang et al. Impairments of enzymes such as insulin degrading enzyme (IDE) ( Miners et al.
2001) and γ -secretases ( Carroll and Li 2016) (for a review on APP processing, see O’Brien and Wong 2011). A β peptides are produced by the sequential enzymatic processing of the amyloid precursor protein (APP) by the β - (BACE1) ( Cai et al. One of the features of Alzheimer’s disease is the accumulation and aggregation of amyloid- β peptides ( A β ) into amyloid plaques ( Iwatsubo et al. Indeed, projection studies of the incidence of Alzheimer’s disease between 20 have indicated that delaying the onset of Alzheimer’s disease by 1, 2, or 5 y could decrease its prevalence by about 10%, 20%, and 50%, respectively ( Mura et al. However, identifying environmental risk factors may represent an alternative strategy to reduce the number of cases. The etiology of Alzheimer’s disease has not yet been clarified, which may explain the lack of effective treatments. Alzheimer’s disease is the most common form of dementia in elderly people and currently afflicts 50 million people worldwide, and this number is expected to double in the coming generation ( OECD 2018).