Experimental Study The Cytotoxic Role Of Advanced Glycation End Products And β-Amyloid Peptide In Alzheimer Disease And Vascular Dementia

Background Aged dementia as a common disease mainly includes Alzheimer disease(AD),Vascular dementia(VaD). recently investigations showed that advanced glycation end products(AGEs) play an important role in aged dementia. Increasing evidence suggested that AGEs regard as a poison products exist in the AD and VaD.This article studied the role of AGEs in AD, VaD and which mechanisms and pathways involved in AGEs.Objective: 1.To explore whether the mechanism of the effect of AGEson PC12 cell induced byβ-amyloid peptide(Aβ)relates to oxidation stress and to study wheather inhibiting the activity of Receptor for advanced glycation end products (RAGE )is a benefit drug target.2. To exam AGEs, Aβin serum of AD, VaD and Acute cerebrovascular disease (ACVD).Methods: 1. PC12 cell were treated by Aβ25-35,then AGEs with different concentration were added to the culture medium for 12 hours ; PC12 cell treated with pancreatic protein enzyme ,then treated by Aβ25-35,then AGEs were added to the culture medium ,the cell activity was measured by MTT assay, the apoptosis situation was detected by flowaytometry and the expressions of RAGE and NF-κB measured by RT-PCR assay .2. Serum Aβwas decaled by radiaimmunaussay, AGEs was tested by enzyme linked immunosorbent assay in clinical diagnosed 7 case of AD, 35 case of VaD and 47 case of ACVD, and 30 normal people were regarded as control group.Results: 1. cell activity decreased with the increase of AGEs concentration ,but the activity increased after treatment with pancreatic protein enzyme ,cell apoptosis rate and expressions of RAGE and nf-κB were elevated with AGEs concentration increasing. 2. The serum Aβand AGEs levels in AD and VaD groups were significantly higher than those in ACVD gropes and control group, AGEs and Aβhave positive relation.Conclusions: 1. The neural toxicity of AGEs was cooperated with Aβ,RAGE triggers the neural toxicity of AGEs to pc12 cell induced by Aβand the molecular mechanisms is connected with the express of NF-κB inducted by RAGE, inhibiting the activity of RAGE can be an effective druy target.2. Increased levels of AGEs and Aβmight be involved in the pathogenesis of aged dementia.