In particular, we propose that loss of function mutations upstream of NF-κB such as ADAM17, SHARPIN, HOIL, or OTULIN affect NF-κB-activity in Alzheimer’s disease (AD) patients, in turn driving anatomical defects such as shrinkage of entorhinal cortex and the limbic system in early AD. This evidence concerns the gene NFKB1 and Alzheimer disease.