MAPT and Alzheimer disease: 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.