Abstract
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.