The current focus of the pharmaceutical industry on treating AD is on activating the immune system to degrade extracellular β-amyloid plaques. However, the degree of side effects has so far been unsatisfactory.
A possibly superior alternative may be to target its main constituent, the amyloid beta (Aβ) peptide, while it is still intracellular. This strategy may be more advantageous, since there is evidence that this is the phase when Aβ is most destructive.
Another intriguing point about targeting intracellular Aβ is that it may not be necessary to seek enzymes to degrade this peptide. The cholesterol-degrading strategy that LysoSENS is currently developing for atheroscerosis may be sufficient.
To elaborate, one way atherosclerosis and AD differ is that the former experiences lysosomal engorgement with undegradable cholesterol but the latter doesn't. But they do seem to have cholesterol in common as a causative agent. In AD, far from being engorged with the material it's supposed to degrade, lysosomes in AD neurons don't seem to have normal access to the material in the first place -- and cholesterol seems to be the culprit, by inhibiting endosomal transport of degradables to lysosomes. Instead of being overwhelmed with the material that the cell needs to eliminate, neuronal lysosomes seem to lose access to it in the first place.
With a common enemy, degradation of cholesterol with tailored enzymes may be the solution in both atherosclerosis and AD. The strategy current LysoSENS research is pursuing for atherosclerosis may ultimately kill two birds with one stone.
