Philadelphia - A glucose deficiency in neuronal cells could be partly responsible for the toxic formation of phosphotau. In Transalational Psychiatry, researchers led by Domenico Praticò from Temple University report that this could be an important factor in the pathogenesis of Alzheimer's (2016; doi:).
With the help of an FGD-PET, many Alzheimer's patients can be involved demonstrate decreased glucose metabolism. The parietal and temporal lobes are particularly affected. The specific pathological significance of this change is, however, not yet clear. The reduced sugar metabolism could be consequence or also (co-) cause of the cognitive decline. The brain is highly dependent on glucose, so that causal relationship between sugar deficiency and nerve degeneration seems at least plausible.
In their study, the scientists used genetically modified mice that accumulated human phosphorylated tau protein in the brain. In order to test how glucose withdrawal affected the course of the disease, the researchers continuously administered 2-deoxyglucose to group of mice. They compared these mice to control group that was not receiving 2-deoxyglucose. The special sugar prevents the absorption of glucose into the brain cells.
After few months, they performed memory tests on the mice. Mice in the experimental group performed significantly worse in these tests. In microscopic examinations, the researchers found that the glucose deficiency led to disruption of synaptic function.
The most important observation was that the amount of phosphorylated tau protein increased due to the glucose deficiency. Phosphorylated tau protein is typically deposited in Alzheimer's disease in the form of neurofibrillary tangles. In further analyzes, the working group was able to identify the protein P38 as the cause of the increase in the cell-damaging protein. Apparently, the glucose deficiency led to an activation of P38.
Based on the results, the researchers suspect that the glucose deficiency is driving factor in the development of Alzheimer's disease. However, if it were possible to interrupt the activation of P38, the formation of the phosphorylated tau protein could be slowed down, the scientists suspect.