In the pathology of AD, failure of insulin and IGF signaling pathways leads to aberrant tau phosphorylation, accumulation of neurofibrillary tangles, senile plaque formation (such as amyloid-beta precursor protein [AβPP] and Aβ peptides), mitochondrial dysfunction, and endoplasmic reticulum (ER) stress, which propagate cell death cascades and disrupt cholinergic homeostasis, ultimately impairing memory formation and cognition48. Here, APP is linked to Alzheimer disease.