Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
School of Public Health, China Medical University, Shenyang, China.
Front Immunol. 2022 Oct 24;13:960906. doi: 10.3389/fimmu.2022.960906. eCollection 2022.
Alzheimer's disease (AD) is a common neurodegenerative disorder without an effective treatment, and results in an increasingly serious health problem. However, its pathogenesis is complex and poorly understood. Nonetheless, the exact role of dysfunctional glucose metabolism in AD pathogenesis remains unclear. We screened 28 core glycolysis-related genes and introduced a novel metric, the glycolysis index, to estimate the activation of glycolysis. The glycolysis index was significantly lower in the AD group in four different brain regions (frontal cortex, FC; temporal cortex, TC; hippocampus, HP; and entorhinal cortex, EC) than that in the control group. Combined with differential expression and over-representation analyses, we determined the clinical and pathological relevance of glycolysis in AD. Subsequently, we investigated the role of glycolysis in the AD brain microenvironment. We developed a glycolysis-brain cell marker connection network, which revealed a close relationship between glycolysis and seven brain cell types, most of which presented abundant variants in AD. Using immunohistochemistry, we detected greater infiltrated microglia and higher expression of glycolysis-related microglia markers in the APP/PS1 AD model than that in the control group, consistent with our bioinformatic analysis results. Furthermore, the excellent predictive value of the glycolysis index has been verified in different populations. Overall, our present findings revealed the clinical and biological significance of glycolysis and the brain microenvironment in AD.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，目前尚无有效的治疗方法，导致其成为日益严重的健康问题。然而，其发病机制复杂，目前仍不完全清楚。尽管如此，糖代谢功能障碍在 AD 发病机制中的确切作用仍不清楚。我们筛选了 28 个核心糖酵解相关基因，并引入了一种新的指标——糖酵解指数，以评估糖酵解的激活程度。在四个不同的脑区（额叶皮层、颞叶皮层、海马体和内嗅皮层）中，AD 组的糖酵解指数明显低于对照组。结合差异表达和过度表达分析，我们确定了糖酵解在 AD 中的临床和病理相关性。随后，我们研究了糖酵解在 AD 脑微环境中的作用。我们构建了糖酵解-脑细胞标志物连接网络，揭示了糖酵解与七种脑细胞类型之间的密切关系，其中大多数在 AD 中存在丰富的变体。通过免疫组织化学检测，我们发现在 APP/PS1 AD 模型中，浸润的小胶质细胞增多，糖酵解相关小胶质细胞标志物的表达水平升高，与我们的生物信息学分析结果一致。此外，糖酵解指数在不同人群中的预测价值良好。综上所述，我们的研究结果揭示了糖酵解及其在 AD 中的脑微环境的临床和生物学意义。
