Therefore, we used pSer46‐MARCKS as a new marker for “ultra‐early‐stage pathology of AD” and found that ultra‐early‐stage necrosis, which was not detected by other previous methods, occurs actively in multiple types of AD mouse models, such as 5xFAD and amyloid precursor protein‐knock in (APP‐KI) mice before the appearance of extracellular Aβ aggregation.15 This evidence concerns the gene APP and Alzheimer disease.