The effect of cannabinoids on APP, BACE1, and ApoE mRNA expression

Alzheimer's disease (AD) is an age-related neurodegenerative condition associated with cognitive decline. The pathological hallmark of this disease is the deposition of β-amyloid protein plaques (Aβ) in the brain, which evoke neuronal cell death and impair inter-neuronal communication. Past studies have suggested that cannabinoids reduce the levels of Aβ in the brain; however, little is known about the mechanisms involved in this process. In this study, the SH-SY5Y cell line was first examined for expression of amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (BACE1), and apolipoprotein E (ApoE), genes involved in Aβ production and clearance. All three genes were expressed and detected in the cell line. We then observed the effects of the endocannabinoid anandamide, a CB1 receptor agonist, on the mRNA expression of APP, BACE1, and ApoE in SH-SY5Y cells. After 48h exposure to anandamide, mRNA levels of APP and BACE1 significantly decreased, which could contribute to reduced Aβ levels. The mechanism of action by which anandamide reduces mRNA levels of APP and BACE1 should be further investigated. ApoE mRNA levels were not found to be significantly changed, suggesting that anandamide does not affect mRNA expression of this gene. The effects of cannabinoids on ApoE levels should be further studied as the effects may occur at a level different from mRNA expression and may even occur via a pathway unrelated to CB1 receptor activation. Keywords: Alzheimer’s disease; β-amyloid; anandamide; amyloid precursor protein; beta-site APP cleaving enzyme 1; apolipoprotein