CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 24, Issue 6, 2025

AD is a demyelinating disease. Myelin damage initiates the pathological process of AD, resulting in abnormal synaptic function and cognitive decline. The myelin sheath formed by oligodendrocytes (OL) is a crucial component of white matter. Investigating AD from the perspective of OL may offer novel diagnostic and therapeutic perspectives.

This study aimed to analyze the association between OL-related genes and Alzheimer's disease (AD) using bioinformatics and verify this association via molecular biology experiments.

The AD datasets were acquired from the Gene Expression Omnibus (GEO) database of NCBI. Consensus clustering was employed to determine the subtypes of AD, followed by evaluating the clinical characteristics of these subtypes. Subsequently, immune infiltration analysis of relevant genes and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted to identify modules and hub genes associated with AD progression. The intersection of genes obtained was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. To narrow down the scope and identify OL-related genes with diagnostic potential, three machine learning algorithms were utilized. In addition, the eXtreme Sum (XSum) algorithm was used to screen small molecule drug candidates based on the connectivity map (CMAP) database. Finally, these identified genes were validated using Real-time fluorescence quantitative PCR (RT-qPCR).

Among the three subtypes of AD, Cluster A and Cluster C exhibited increased levels of Braak and neurofibrillary tangles compared to Cluster B. The proportion of females was greater than that of males among the three subclasses of AD. There were no significant differences in age among the three subclasses, but significant differences in gene expression existed. Through WGCNA analysis, 108 genes were identified. Among these, 16 genes were identified as shared genes by the least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machines (SVM) algorithms, and logistic regression further determined 11 genes. The establishment of a nomogram demonstrated the significance of these 11 genes in AD. The “XSum” algorithm revealed five drugs with therapeutic potential for AD. RT-qPCR analysis revealed the upregulation and downregulation of the highlighted genes. According to this study, 11 genes related to OL were also found to be associated with immune cell infiltration in AD patients. These genes demonstrated potential diagnostic value for AD. Additionally, we screened five small molecular drugs that exhibit potential therapeutic effects on AD.

This research provides a new perspective for personalized clinical management and treatment of AD.

The goal of this to demonstrate the impact of heavy and chronic cannabis use on brain potential functional control, reorganization, and plasticity in the cortical area.

23 cannabis users were convened in 3 groups of users. The first group included 11 volunteers with an average of 15 joins/day; the second group included 6 volunteers with an average of 1.5 joins/day; the third group included 6 volunteers with an average of 2.8 joins/week. Besides, 6 healthy volunteers in the control group, All healthy and cannabis users underwent identical brain BOLD-fMRI assessments of their motor function. Besides, neuropsychological and full biological assessments were achieved.

BOLD-fMRI maps of motor areas were obtained, including quantitative evaluation of the activations in the motor area. A statistical analysis of various groups was achieved.

Groups of chronic cannabis addiction of varying level of use were setup. Namely heavy, moderate and low users groups; doses have been shown to have systematically equivalent effects on the control of brain motor function. Indeed, the BOLD-fMRI shows a remarkable sensitivity to brain plasticity and reorganization of the functional motor control of the studied cortical area, and such variation was not shown. Specific elucidation of the effect of cannabis effect in this unique function should clarify further protective pharmacological effects. This might illuminate the use of neuronal resources to prepare processes for pharmacological use and pharmaceutical forms. This suggests exploring any potential cannabis pharmaceutical form in diseases involving motor impairments.