APP and Alzheimer disease: While several trisomic genes have been implicated in AD pathology or memory impairments, including amyloid precursor protein (APP) [21, 23, 30, 78], dual specificity tyrosine phosphorylation regulated kinase 1 A (DYRK1A) [25, 43], transmembrane serine protease 2 (TMPRSS2) [2], and 4 of the 6 known genes encoding Type I interferon receptors [24, 28, 35, 87], little genomic information related to excitatory cortical projection neurons during the critical stages of pathogenesis is available.