We found that APP interacts with the S protein of SARS-CoV-2, promotes the cellular entry of the virus, and exacerbates Aβ-associated pathology in the APP/PS1 mouse model of AD, which can be inhibited by N-terminal APP blocker AY51, a peptide analog of 6KApoEp [32, 33]. The gene discussed is APP; the disease is Alzheimer disease.