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Current Alzheimer Research - Volume 22, Issue 6, 2025

Volume 22, Issue 6

Volume 22, Issue 6, 2025

    • The Interaction between Oligodendrocytes and Aβ in Alzheimer's Disease

      https://doi.org/10.2174/0115672050401966250625171338

      Oligodendrocytes (OLs) are the primary myelinating cells in the central nervous system (CNS), responsible for maintaining the rapid conduction of nerve signals and ensuring neuronal stability through metabolic and nutritional support. Recent studies have reported that OLs are also involved in the development and progression of Alzheimer's disease (AD), particularly in the production and clearance of amyloid-beta (Aβ), exhibiting complex and critical regulatory functions. While traditional research has predominantly focused on the roles of neurons and microglia in Aβ metabolism, recent evidence indicates that OLs engage in a complex bidirectional interaction with Aβ in AD. On the one hand, OLs can produce Aβ, frequently generating aggregated and highly toxic Aβ, which contributes to plaque expansion and disease progression. On the other hand, neuron-derived Aβ exerts a concentration-dependent dual effect on OLs. At high concentrations, it induces oxidative stress and cell apoptosis, while at low concentrations, it promotes their differentiation and myelin repair functions. Therefore, OLs serve as both a “source” and a “target” of Aβ production and response, making them a key factor in AD pathogenesis. This review discusses the interaction between OLs and Aβ in AD, aiming to provide new perspectives on targeting OLs for AD therapy. Given the dual role of OLs in Aβ metabolism, targeting OLs dysfunction and the regulatory mechanisms underlying Aβ production and clearance could provide novel therapeutic strategies for AD. Future research should investigate the roles of specific OL populations (including oligodendrocyte precursor cells (OPCs), pre-myelinating OLs, and mature OLs) in Aβ generation and metabolism, focusing on the signaling pathways involved. Additionally, the molecular mechanisms by which OLs regulate other glial cells, such as astrocytes and microglia, through intercellular signaling to facilitate Aβ clearance and maintain neuroglial homeostasis warrant further exploration.

    • Comprehending Alzheimer's Disease: Molecular Mechanisms and Treatment Strategies

      https://doi.org/10.2174/0115672050368798250626075628

      Alzheimer's disease (AD) is a complex neurodegenerative disorder and a growing global health challenge, driven by increasing life expectancy and an aging population. This review provides a comprehensive exploration of AD pathophysiology, integrating current hypotheses such as the amyloid cascade, tau protein pathology, cholinergic dysfunction, neuroinflammation, vascular contributions, and potential infection-related mechanisms. The multifactorial etiology of AD, encompassing genetic predispositions and environmental factors, underscores its intricate nature. This study delves into the diagnostic advancements, including the identification and utilization of biomarkers for early detection and disease monitoring. Therapeutic approaches are critically evaluated, highlighting anti-amyloid and anti-tau strategies, alongside emerging innovations in stem cell therapy and nanobiotechnology. A detailed examination of clinical trials offers insights into the achievements and setbacks of translating research into effective treatments. By synthesizing epidemiological trends, molecular mechanisms, and therapeutic developments, this review aims to advance our understanding of AD and foster collaborative efforts to develop transformative solutions. It emphasizes the urgency of addressing this multifaceted disease, presenting a nuanced perspective on its complexity while illuminating future directions for research and clinical practice.

    • Alterations of (), (), and () Genes in the Frontal Cortex in an Ischemic Model of Alzheimer's Disease with Long-Term Survival

      https://doi.org/10.2174/0115672050385480250619045022
      Introduction

      Currently, there is no information on changes in the (), ), and () genes in the frontal cortex after brain ischemia with animal survival for 2 years. Furthermore, it is not known whether the and genes possess any influence on neurons in the frontal cortex due to ischemia.

      Aims

      The goal of the investigation was to evaluate alterations in the behavior of , and genes in the frontal cortex following ischemia with survival of 2 years.

      Materials and Methods

      Gene expression was assessed using an RT-PCR protocol at 2-30 days and 6-24-months after ischemia.

      Results

      gene expression after ischemic injury was lower than the control group during 7-30- days and 18 months, whereas overexpression was noted after 2 days, 6-, 12- and 24 months. In the case of gene expression, it was lower than the control group for 2-7 days and higher than the control throughout the remaining time after ischemia. Increased expression of the gene was observed except on days 7-30 following ischemia when its expression was lower compared to control values.

      Discussion

      The data seem to indicate that the observed changes in gene expression may reflect the activation and inhibition of different mechanisms involved in the advancement of neurodegeneration after ischemia.

      Conclusion

      Overexpression of gene is likely to be associated with the induction of neuroprotective phenomena, whereas overexpression of and genes can cause harmful effects.

    • Effective Analysis of Alzheimer's Disease and Mechanisms of Methyl-4-Hydroxybenzoate using Network Toxicology, Molecular Docking, and Machine Learning Strategies

      https://doi.org/10.2174/0115672050399031250623062112
      Introduction

      Nowadays, the large increase in environmental pollutants has led to the occurrence and development of an increasing number of diseases. Studies have shown that exposure to environmental pollutants, such as methyl-4-hydroxybenzoate (MEP) may lead to Alzheimer's disease (AD). Therefore, the purpose of this study was to elucidate the complex effects and potential molecular mechanisms of environmental pollutants MEP on AD.

      Methods

      Through exhaustive exploration of databases, such as ChEMBL, STITCH, SwissTargetPrediction, and Gene Expression Omnibus DataSets (GEO DataSets), we have identified a comprehensive list of 46 potential targets closely related to MEP and AD. After rigorous screening using the STRING platform and Cytoscape software, we narrowed the list to nine candidate targets and ultimately identified six hub targets using three proven machine learning methods (LASSO, RF, and SVM): CREBBP, BCL6, CXCR4, GRIN1, GOT2, and ITGA5. The “clusterProfiler” R package was used to conduct GO and KEGG enrichment analysis. At the same time, we also constructed disease prediction models for core genes. At last, six hub targets were executed molecular docking.

      Results

      We derived 46 key target genes related to MEP and AD and conducted gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. MEP might play a role in AD by affecting the pathways of neuroactive ligand-receptor interaction. Nine genes were screened as pivotal targets, followed by machine learning methods to identify six hub targets. Molecular docking analysis showed a good binding ability between MEP and CREBBP, BCL6, CXCR4, GRIN1, GOT2 and ITGA5. In addition, changes in the immune microenvironment revealed a significant impact of immune status on AD.

      Discussions

      This study revealed that MEP may induce AD through multiple mechanisms, such as oxidative stress, neurotoxicity, and immune regulation, and identified six core targets (CREBBP, BCL6, ) and found that they are related to changes in the immune microenvironment, such as T cells and B cells, providing new molecular targets for AD intervention.

      Conclusion

      Overall, CREBBP, BCL6, CXCR4, GRIN1, GOT2, and ITGA5 have been identified as the crucial targets correlating with AD. Our findings provide a theoretical framework for understanding the complex molecular mechanisms underlying the effects of MEP on AD and provide insights for the development of prevention and treatment of AD caused by exposure to MEP.

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