For example, peripheral metabolic derangements from insulin resistance or T2DM may lead to desensitization of neuronal insulin receptors, which may in turn lead to decreased clearance of beta amyloid (Aβ) peptide and increased hyperphosphorylation of τ protein, which forms neurofibrillary tangles and damage the brain, but which of these are clinically relevant is unclear (Gasparini et al., 2001). Here, INSR is linked to Insulin resistance.