Fig. 1

Glucose metabolism and its involvement in AD. There are several mechanisms in which, directly or indirectly, glucose is involved in AD. (i) As a potential mechanism, a diagram with a general metabolic dysfunction that leads to an increased insulin resistance, and consequently, lower glucose uptake; (ii) in post-translational modifications in which glucose or glycans are required, such as methylation. These modifications also alter others post-translational modifications, such as phosphorylation and ubiquitination, which leads to tau aggregation and (iii) through the generation of ATP, that is released to the extracellular, where it can be sensed by microglia, and then transformed into adenosine. This adenosine suppresses neuronal activity and in the long term, causes synaptic dysfunction. ER, endoplasmic reticulum; ADP, adenosine di-phosphate; A2AR, adenosine receptor type 2; GLUT, glucose transporter ; PHF, paired helical filaments; CDK5, cyclin-dependent kinase type 5; CD73: 5′-nucleotidase; CD39, ectonucleoside triphosphate diphosphohydrolase-1