Ren_2020_Mol.Med.Rep_22_2063

Alzheimer's disease (AD) is a chronic neurodegenerative, and abnormal aggregation of the neurotoxic beta amyloid (Abeta) peptide is an early event in AD. The present study aimed to determine the correlation between the nicotinic acetylcholine receptor alpha7 subunit (alpha7 nAChR) and Abeta in the brains of patients with AD, and to investigate whether the increased expression levels of the alpha7 nAChR could alter the neurotoxicity of Abeta. The expression levels of alpha7 nAChR and Abeta in the brains of patients with AD and healthy brains were analyzed using immunofluorescence. Moreover, SHSY5Y cells were used to stably overexpress or silence alpha7 nAChR expression levels, prior to the treatment with or without 1 micromol/l Abeta142 oligomer (AbetaO). The mRNA and protein expression levels of alpha7 nAChR, synaptophysin (SYP), postsynaptic density of 95 kDa (PSD95) and synaptosomalassociated protein of 25 kDa (SNAP25) were subsequently analyzed using reverse transcriptionquantitative PCR and western blotting. In addition, the concentration of acetylcholine (ACh) and the activity of acetylcholinesterase (AChE) were analyzed using spectrophotometry, while the cell apoptotic rate was determined using flow cytometry. The expression of Abeta in the brains of patients with AD was found to be significantly increased, whereas the expression of alpha7 nAChR was significantly decreased compared with the healthy control group. In vitro, the expression levels of alpha7 nAChR were significantly increased or decreased following the overexpression or silencing of the gene, respectively. Consistent with these observations, the mRNA and protein expression levels of SYP, PSD95 and SNAP25 were also significantly increased following the overexpression of alpha7 nAChR and decreased following the genetic silencing of the receptor. In untransfected or negative control cells, the expression levels of these factors and the apoptotic rate were significantly reduced following the exposure to AbetaO, which was found to be attenuated by alpha7 nAChR overexpression, but potentiated by alpha7 nAChR RNA silencing. However, no significant differences were observed in either the ACh concentration or AChE activity following transfection. Collectively, these findings suggested that alpha7 nAChR may protect the brains of patients with AD against Abeta, as alpha7 nAChR overexpression increased the expression levels of SYP, SNAP25 and PSD95, and attenuated the inhibitory effect of Abeta on the expression of these synaptic proteins and cell apoptosis. Overall, this indicated that alpha7 nAChR may serve an important neuroprotective role in AD.