It is believed that this hydrophobicity promotes rapid conformationalchange and protein misfolding into the β-sheet structures andtoxic aggregation.5−7 Notably, Abeta-pE3 is found as a major species depositedin the plaques and vessels of AD and Down syndrome patients.8−11 Abeta-pE3 is also deposited in the brains of several preclinicalanimal models, albeit at the later stages compared to human cases.12 Additionally, this post-translational modificationof Abeta is more neurotoxic than other Abeta counterparts.12,13. Here, APP is linked to Down syndrome.