We found that the level of NLGN1 is decreased in the hippocampus of aMCI and AD patients and in young 3xTg-AD female mice, and that hippocampal Aβo1-42 injections decreased neuronal count in the DG and induced spatial learning deficits predominantly in Nlgn1 knockout (KO) mice. Here, NLGN1 is linked to Alzheimer disease.