Effect And Mechanism Of Aβ_20-29 Peptide In Transgenic Mice Of Alzheimer’s Disease

Background and objectiveAlzheimer’s disease （AD） is one of the most common etiological factorsof dementia in elderly people. AD is characterized by progressive memoryloss, life dysfunction and personality change. During AD, the characteristicpathological change is the wildly distributed formation of senile plaques （SP）,neurofibrillary tangles （NFT） and neuronal loss in the brain tissue. Althoughthe exact etiology and pathogenesis of AD have been not well established,current evidence indicates that the amyloid-beta （Aβ） aggregation, amyloidplaque formation and its neurotoxicity may play an important role in theformation and development of AD. It has been reported that apolipoprotein E（ApoE） may bind to Aβ forming ApoE/Aβ which contributes to Aβaggregation, fibrillization, deposition and SP formation. Therefore, ApoEplays a critical role in the development of AD. Our recent in vitro experimentsshowed that the Aβ_20-29peptide can competitively block the ApoE/Aβinteraction, reduce the Aβ aggregation, fibrillization, deposition and its neurotoxicity in APPswe/PS1dE9transgenic mice. However, it is unknownwhether Aβ_20-29peptide can effectively improve the AD cognitive impairmentor reduce the damage of brain. The purpose of this study is to determine theeffects of Aβ_20-29on the development of AD, and to discover its potentialmechanism in APPswe/PS1dE9transgenic mice. What’s more, the study mayprovide a theoretical basis and experimental basis for development of newprevention AD drugs.MethodThe female juvenile （16W） APPswe/PS1dE9mice were randomly dividedinto Aβ_20-29treatment group and vehicle group. The spatial learning and memoryabilities of Aβ_20-29treatment group and vehicle group of mice were assessed byMorris water maze test; ELISA test was applied to observe the brain ofAPPswe/PS1dE9mice of Aβ_1-40,42, expression level; Western blot method（Western blotting） was applied to observe the changes in the brain ofAPPswe/PS1dE9mice of apoE, amyloid precursor protein （APP） andinflammation.Results（1） Morris water maze test showed that the spatial learning wassignificantly decreased （F （1,14）=12.75, P <0.01） in the Aβ_20-29treatment groupof APPswe/PS1dE9mice as compared with vehicle group, but the spatialmemory capacity significantly increased （P <0.01）. These data suggest that theeffects of Aβ_20-29significantly improve learning disabilities and spatial memoryimpairment in APPswe/PS1dE9mice;（2） ELISA experimental results showedthat the soluble （P<0.01） and insoluble （P<0.05） Aβ_1-42levels in the Aβ_20-29treatment group APPswe/PS1dE9mice of brain were significantly lower thanvehicle group. And Aβ_1-40level in in the Aβ_20-29treatment group APPswe/PS1dE9mice were also significantly lower （P<0.01） than the vehiclegroup. The results indicated that the effects of Aβ_20-29significantly reduceAβ_1-40,42level in APPswe/PS1dE9mice;（3） Western blotting experimentsshowed that APP level in the Aβ_20-29treatment group APPswe/PS1dE9mice ofbrain were significantly lower （P<0.01） than vehicle group mice. The resultsindicated that the effects of Aβ_20-29significantly reduce APP level inAPPswe/PS1dE9mice. Compared with vehicle group mice, the content of ApoEin Aβ_20-29treatment group APPswe/PS1dE9mice of brain was significantlydeclined （P<0.01）. The results indicated that the effects of Aβ_20-29significantlyreduce ApoE level in APPswe/PS1dE9mice. What’s more, GFAP （P<0.05） aswell as Iba-1（P<0.01） were significantly declined in Aβ_20-29treatment groupAPPswe/PS1dE9mice of brain as compared with vehicle group mice. Theresults indicated that the effects of Aβ_20-29significantly improve inflammation inAPPswe/PS1dE9mice.Conclusion（1） Aβ_20-29significantly improve learning disabilities and spatial memoryimpairment in APPswe/PS1dE9mice.（2） Aβ_20-29significantly reduce APP,Aβ_1-40,42level in APPswe/PS1dE9mice.（3） Aβ_20-29significantly reduce ApoElevel in APPswe/PS1dE9mice.（4） Aβ_20-29significantly improve inflammationin APPswe/PS1dE9mice. To sum up, the effects of Aβ_20-29significantlyimprove learning disabilities and spatial memory impairment, and reduce theAβ aggregation and its neurotoxicity by its ability of competitively bindingwith ApoE. For this reason, we think Aβ_20-29peptide may be used for theprevention and treatment of AD progression.