PSEN1 and Alzheimer disease: Despite its effectiveness in terms of improving mushroom spine morphology and TRPC6-mediated SOCE in PS1-KI and APP-KI hippocampal neurons and rescuing long-term potentiation in the APP-KI mouse model of AD, NSN21778 is found to have a rather poor pharmacokinetic profile and a low penetration of the blood–brain barrier [14].