INSR and Insulin resistance: For instance, for AD, TOMM40 has been associated with mitochondrial dysfunction and neuroinflammation, which can exacerbate insulin resistance [98], while APOE, particularly the APOE-ε4 allele, is a well-established risk factor for late-onset AD and has been shown to interfere with insulin receptor signaling, trapping insulin receptors in endosomes and impairing their function [99].