To define the pathological activities of various APP and Tau fragments resulting from δ-secretase cleavage, we injected the hippocampus of wild-type mice with AAV expressing truncates separately or in combination and found that fragments of δ-secretase cleavage, APP (586-695) and Tau (1-368), additively drive AD pathogenesis and cognitive dysfunction. Here, MAPT is linked to Alzheimer disease.