Screening and In Vivo Validation of Key Genes Involved in Myelin Damage in Alzheimer's Disease

Myelin sheath damage exacerbates cognitive deterioration in Alzheimer's disease (AD). This study identified 11 key genes related to myelin sheath damage between AD and control samples based on the GSE118553 dataset, and their expression was verified in the AD mouse model. Furthermore, the damage to myelin and synapses as well as the expression of the insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK3β) signaling pathway proteins were observed by transmission electron microscopy and molecular biology techniques. The results confirmed that the expression of 8 out of 11 key genes was downregulated in mice with AD, which showed amyloid β-protein (Aβ) deposition, tau hyperphosphorylation, myelin and synaptic damage, and an abnormal expression of IRS-1/PI3K/Akt/GSK3β signaling and glucose transporter1/3 (GLUT1/3). This study provides a basis for the in-depth exploration of the gene regulatory mechanisms of myelin sheath injury in AD.