The Study On Caspr Function In Alzheimer’s Disease By Inducing Autophagy

Objective: Alzheimer’s disease(AD)is a degenerative disease of the central nervous system.It is mainly manifested as progressive cognitive dysfunction.However,over the past several years,neuroimaging studies have implicated obvious abnormalities in white matter,which have been proved to be associated with demyelination changes.The contactin-associated protein(Caspr)family participates in nerve excitation and conduction,and neurotransmitter release in myelinated axons.The absence of Caspr can lead to demyelination changes.Here we proposed to study the mechanism of Caspr underlying cognitive impairment by analyzing the relationship between Caspr and cognitive impairment in AD patients.Methods: 42 AD patients were divided into mild AD group and moderate-severe AD group according to the CDR-SB with 25 healthy elderly volunteers served as a control group in this study.Expression of Casprm RNA was detected by RT-PCR.Expression of microtubule-associated protein light chain(LC3)was detected by ELISA.The relationship between expression of Caspr m RNA and LC3 was analyzed.Expression of LC3 in the cerebral cortex of Caspr knockout(Caspr-/-)and their littermate wildtype(Caspr+/+)was detected by Western blot and immunofluorescence staining.The Caspr and empty vector plasmids were transfected into HEK293 cells to investigate the expression of LC3.Results:1)MMSE scores were significantly less while ADL scores were significantly more in AD patients than in control subjects(P<0.01).2)The expression of Caspr m RNA was significantly lower while that of LC3 was significantly higher in in AD patients than in control subjects(P<0.01).3)The expression of Caspr m RNA was positively related with MMSE scores(r=0.716,P<0.001).The expression of LC3 was negatively related with MMSE scores(r=-0.707,P<0.001).The expression of Caspr m RNA was positively related with LC3(r=-0.416,P<0.01).4)Deletion of Caspr increased the number of LC3-positive neurons and the ratio of LC3Ⅱ/LC3Ⅰ.5)The LC3 of HEK293 cells overexpressed Caspr was significantly lower than in control group.Conclution: Caspr participates in the pathogenesis of AD by inducing autophagy.Caspr is promising as a marker of peripheral blood in Alzheimer’s disease.