A new study published in the journal Molecular and Cellular Proteomics reveals that a team of German researchers has identified why the signals between nerves cells are disrupted in Alzheimer's patients following abnormal protein deposits in their brains.
They varied the amount of APP protein and related proteins associated with Alzheimer's disease in cell cultures, and then analysed how this manipulation affected other proteins in the cell. The result: the amount of APP present was related to the amount of an enzyme that is essential for the production of neurotransmitters and therefore for communication amongst nerve cells.
Proteomics: analysing all the proteins of the cells at once
Abnormal protein able to curb neurotransmitter production
"One candidate has particularly caught our attention, this being the enzyme methionine adenosyltransferase II, alpha, MAT2A for short", Thorsten Müller said. Among other things, the enzyme is crucially involved in the production of neurotransmitters. Low-APP cells contained less MAT2A than the reference cells. To confirm the connection between the "Alzheimer's protein" APP and the neurotransmitter-producing MAT2A, the team studied tissue samples from the brains of deceased Alzheimer's patients and from healthy individuals. In the tissue of the Alzheimer's patients there was less MAT2A than in the healthy samples. These results suggest that APP and MAT2A concentrations are related and are linked to the synthesis of neurotransmitters. "Our results point to a new mechanism by which the defective cleavage of the APP protein in Alzheimer's disease could be directly related to altered neurotransmitter production", Müller said. "As a result, the signal transduction of nerve cells could be disrupted, which, over an extended period, could possibly also cause the death of cells."