Indeed, these carriers tend to develop the disease later than others, but when that happens, it progresses more rapidly and does not respond to medication. Therefore, the bottom line is that carriers of the mutated gene have a greater risk than others for disease progression.
The reason for this anomalous situation has been a puzzle for a long time, but the studies by the Hebrew University scientists solved it by finding the explanation for this increased risk, thereby offering as well a possible new therapeutic solution.
At the Wolfson Center for Structural Biology at the Hebrew University, the researchers found that the mutation in the BChE-K gene damages the very end, or tail, of the resultant mutant enzyme protein. This tail is the part of BChE which is important for protection from the Alzheimer's disease plaques. It does this by interacting with the Alzheimer's disease β-amyloid protein and preventing it from precipitating and forming those brain plaques which are the neuropathological hallmark of this disease.
To compare the normal protein to the K mutant, the researchers used synthetic tails of the normal and the K proteins, as well as engineered human BChE produced in the milk of transgenic goats at a U.S. company, Pharmathene. The goat- produced protein is prepared at Pharmathene for the U.S. military as protection from nerve gas poisoning (a result of earlier research at the Hebrew University). It was much more stable and efficient than the mutant protein, which suggests that the BChE-K carriers’ susceptibility to Alzheimer’s could be substantially improved by treating them with the engineered normal protein that is produced in the milk of the transgenic goats.