APP and Cognitive impairment: The 5xFAD murine TgAD model containing five familial AD mutations; including three amyloid mutations and two presenilin 1 (PSEN1) mutations [APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), and PSEN1 L286V] exhibit substantial Aβ42 peptide generation, amyloid plaque deposition, astrogliosis, and cognitive impairment by 7 months of age and also exhibit deficits in Shank3 at this time point [(25); Figure 1].