PRKN and Alzheimer disease: In the hippocampus and cortex of AD patients, the E3 ubiquitin ligase Parkin was found to colocalize with intraneuronal Aβ4293 and in a triple transgenic AD mouse, Parkin expression was shown to decrease Aβ levels and extracellular plaque deposition,94 suggesting it may mediate at least some of the UPS's Aβ42 clearing activity.