Serological Expression Of Midkine In Alzheimer’s Disease And Its Regulatory Rule In The Proliferation Of Mouse Neural Stem Cells In Vitro

ObjectivesAlzheimer’s Disease(AD)is a prevalent neurodegenerative disorder with a complex pathogenesis and no definitive treatment to date.However,neural stem cells(NSCs)have the potential to self-renew,proliferate,migrate,and differentiate,thereby becoming a potential target for AD therapy.In recent years,Midkine(MK),a growth factor,has gained increasing attention for its role in various cell growth processes and its importance in the nervous system and inflammatory diseases.Our study mainly investigated the role and biological mechanism of MK in the proliferation process of NSCs,and further explored the expression characteristics of MK in the serum of Alzheimer’s disease(AD)patients and its clinical significance,aiming to provide new scientific evidence for early screening and treatment of Alzheimer’s disease.MethodsWe obtained mouse NSCs for in vitro experiments using primary neurosphere culture method and examined the influence of MK on the proliferation and differentiation of NSCs through in vitro experiments.Using immunocytochemical fluorescence staining,Western Bloting,RT-PCR and other experimental methods,we detected the impact of MK on NSC proliferation and the expression of related genes.Simultaneously,we also took the elderly undergoing regular physical examinations and outpatients with AD from the affiliated central hospital as our research subjects,collected blood samples,and measured the MK content in the serum through an ELISA test kit.ResultsWe found that after knocking out MK,the in vitro neurosphere proliferation ability of NSCs significantly decreased,while the proliferation condition of NSCs supplemented with MK significantly improved.Additionally,we discovered that adding MK to the culture medium can activate its receptor PTPζ,stimulate the Akt proliferation signaling pathway,induce the proliferation of NSCs,and inhibit apoptosis.In terms of MK detection in the serum,we found that MK was not detected in the serum of normal elderly people over 60 years old who underwent a physical examination;MK was present in the serum of some patients in the MCI group,and MK was detected in the serum of all patients in the AD group,with the content of serum MK positively correlated with the severity of the disease.ConclusionIn summary,our study concludes that MK plays a critical role in the proliferation of neural stem cells by activating its receptor PTPζ and stimulating the Akt proliferation signaling pathway,thereby inducing NSC proliferation and inhibiting apoptosis.Additionally,MK has clinical relevance in the diagnosis and evaluation of AD and MCI,potentially serving as an effective serum biomarker for early-stage AD.These findings contribute to our understanding of the pathogenesis of AD and provide a new perspective for the prediction and evaluation of AD patients and the assessment of therapeutic efficacy.