ApoE4 is the best known genetic risk factor for Alzheimer's disease, but, until now, the mechanism by which it increases that risk has remained a mystery. The key finding of the current study relates to apoE4's tendency to be broken down into toxic fragments when it is produced in neurons, the brain cells responsible for cognitive functions.
Proteins can be broken into small pieces by enzymes known as proteases in a process termed proteolysis. While the degradation of proteins is important for many cell processes, it can be harmful when it occurs inappropriately, not only because it destroys the protein, but also because abnormally high levels of fragments can damage cells.
In the new study, involving the examination of genetically engineered mice, Gladstone researchers have established that: