Effects of ADAM10 gene deletion on APP shedding, neuronal synapse and cognitive function in adult mice

A disintegrin and metalloprotease 10 (ADAM10) is a member of the large family of ADAMs (a deintegrin and metalloproteinases) which is involved in the hydrolysis of various cellular receptors and signaling molecules (such as APP etc.) for regulating the development of various organs and tissues of the body. ADAM10 is an Alzheimer's disease (AD) susceptibility gene, so we used the adult neural cell-specific ADAM10 gene knockout ( ADAM10 cKO) mice to study the effects of the ADAM10 gene on APP shedding, neuronal synapse, and cognitive function in adult mice. Our study revealed that deletion of the ADAM10 gene resulted in the increase of sAPPβ, CTFβ, total Aβ peptide, and the reduction of sAPPα and CTFα in the brains of adult mice. Moreover, the expression of the synaptophysin in the hippocampus and cortex of mice brain decreased to different degrees, while the expression of post-synaptic dense protein-95(PSD-95) in the hippocampal CA1 decreased. Synaptic ultrastructure was abnormal, and long-term potentiation (LTP) induction was abnormal, which had a serious effect on the normal nerve cells, resulting in learning and memory impairment in the mice. These studies help to deepen our understanding of the function of the ADAM10 gene and provide a theoretical basis for the prevention and treatment of AD.