MAPT and Alzheimer disease: Small molecule protein degradersgenerally consist of a target binding warhead, a linker, and a E3ligase binding ligand, thereby giving rise to a large molecular weightunsuitable as a CNS drug.43 Indeed, inour pilot trial via intraperitoneal injection, we observed neithersignificant improvement of memory function nor reduction of Aβdeposits and p-tau in AD mice treated with PRZ-18002, partly due toits large molecular weight hampering BBB penetration.