The significance of glycolysis index and its correlations with immune infiltrates in Alzheimer's disease.
The significance of glycolysis index and its correlations with immune infiltrates in Alzheimer's disease.
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DOI：
10.3389/fimmu.2022.960906
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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阿尔茨海默病（Alzheimer's disease，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，并导致日益严重的健康问题。然而，其发病机制复杂且知之甚少。尽管如此，糖代谢异常在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，并引入了一个新的度量标准，糖酵解指数，以估计糖酵解的激活。与对照组相比，AD组4个不同脑区（额叶皮质FC、颞叶皮质TC、海马HP和内嗅皮质EC）的糖酵解指数均显著降低。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。我们开发了糖酵解-脑细胞标记物连接网络，揭示了糖酵解与7种脑细胞类型之间的密切关系，其中大多数在AD中呈现丰富的变体。使用免疫组织化学，我们检测到APP/PS1 AD模型中浸润的小胶质细胞和糖酵解相关小胶质细胞标记物的表达高于对照组，与我们的生物信息学分析结果一致。此外，糖酵解指数的良好预测价值已在不同人群中得到验证。总的来说，我们目前的研究结果揭示了糖酵解和脑微环境在AD中的临床和生物学意义。
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.
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DOI：
10.1038/nrneurol.2017.185
发表时间：
2018-03
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Arnold SE;Arvanitakis Z;Macauley-Rambach SL;Koenig AM;Wang HY;Ahima RS;Craft S;Gandy S;Buettner C;Stoeckel LE;Holtzman DM;Nathan DM
通讯作者：
Nathan DM
DOI：
10.1073/pnas.1507125112
发表时间：
2015-06-09
影响因子：
11.1
作者：
Darmanis S;Sloan SA;Zhang Y;Enge M;Caneda C;Shuer LM;Hayden Gephart MG;Barres BA;Quake SR
通讯作者：
Quake SR
影响因子：
15.9
作者：
Benigni, F;Atsumi, T;Bucala, R
通讯作者：
Bucala, R
影响因子：
14
作者：
通讯作者：
--
影响因子：
3.9
作者：
Croteau, E.;Castellano, C. A.;Cunnane, S. C.
通讯作者：
Cunnane, S. C.