The effect of cadmium on Aβ levels in APP/PS1 transgenic mice

Abstract

Cadmium (Cd), which is a poisonous trace element, has been reported extensively to lead to morphological and biochemical abnormalities of the central nervous system, memory loss and mental retardation. We studied the Alzheimer's disease-related toxicity of Cd in a mouse model [amyloid precursor protein (APP)/ presenilin 1 (PS1) transgenic mice, dual transfection of APP695swe and mutated PS1 genes]. Behavioral changes were detected using the Morris water maze test. The β-amyloid protein (Aβ) levels were determined using immunohistochemistry and ELISA. The free zinc ion concentration in mouse brain was determined using autometallography. The protein expression of α-secretase, soluble APPα (sAPPα) and neutral endopeptidase (NEP) in the mouse cerebral cortex and hippocampus was detected using western blotting. We found that Cd treatment increased the latency and distance of the platform search and reduced the number of platform crossings. The number and size of senile plaques in the brains of Cd-treated mice were significantly increased. The levels of Aβ(1-42) and free zinc ions were increased. The expression of ADAM10, sAPPα and NEP protein was reduced. We speculated that Cd reduced the expression of ADAM10, sAPPα and NEP protein, which caused an increase in the levels of Aβ(1-42) and free zinc ions and led to the accelerated Aβ deposition found in the experimental animals and their abnormal behavior.

Cadmium-induced cell death of basal forebrain cholinergic neurons mediated by muscarinic M1 receptor blockade, increase in GSK-3β enzyme, β-amyloid and tau protein levels

“…Cadmium treatment also increased Aβ 1-40 and Aβ 1-42 levels with higher increase in Aβ 1-42 levels, which was reported to be more fibrillogenic and displays higher neurotoxicity in vivo than Aβ 1-40 (Klein et al 1999). These results are according to previously reported data (Li et al 2012;Smedman et al 1997). Cadmium treatment of silenced βAPP cells attenuated caspase 3/7 activation, LDH release and cell viability reduction observed with cadmium alone, which proves that Aβ proteins mediated the cell death induced by cadmium on cholinergic neurons.…”

“…Otherwise, cadmium has been described to activate glycogen synthase kinase 3 beta (GSK-3β; Wang et al 2009), increase amyloid beta (Aβ) protein production from amyloid beta precursor protein (βAPP; Li et al 2012;Smedman et al 1997) and tau filament formation (Jiang et al 2007). These effects have been related to the induction of cell death in basal forebrain cholinergic neurons and AD (Hawkes et al 2005;Kar et al 2004;Zheng et al 2002); thus, they could mediate the more pronounced basal forebrain cell death observed after cadmium treatment.…”

Dendropanax morbifera Léveille extract ameliorates cadmium-induced impairment in memory and hippocampal neurogenesis in rats

“…In addition, cadmium decreases cognitive functions in humans [32] and induces neuronal death in basal forebrain cholinergic neurons [33]. Furthermore, cadmium treatment facilitates an increase in the number and size of senile plaques and promotes memory impairments [34]. In the present study, the administration of cadmium with DMS ameliorated the decreased locomotor activity and improved the DI in a novel-object recognition test.…”

Cadmium and Alzheimer’s disease mortality in U.S. adults: Updated evidence with a urinary biomarker and extended follow-up time

“…Currently, a small body of experimental evidence has shown that cadmium treatment could reduce the learning and memory capacities of mice genetically susceptible to AD (Li et al, 2012). Cadmium-treated animals also had lower levels of brain α-secretase and neutral endopeptidase (Li et al, 2012), as well as higher levels of amyloid precursor protein (Ashok et al, 2015). Together, these conditions caused increased amyloid beta production, decreased amyloid beta degradation, and the formation of larger and more numerous senile plaques.…”