MAPT and Alzheimer disease: While PSEN1 mutation carriers often exhibit significant Aβ and tau and burden, hippocampal atrophy, and brain hypometabolism,21, 22APOE‐Ch carriers with PSEN1 mutation have been shown to be protective against AD, with one homozygous individual exhibiting minimal tau pathology, hippocampal atrophy, and hypometabolism despite the presence of a PSEN1 mutation.20, 21