Alzheimer's disease (AD) has characteristic neuropathological abnormalities including regionalized neurodegeneration, neurofibrillary tangles, amyloid beta (Aβ) deposition, activation of pro-apoptotic genes, and oxidative stress. As the brain functions continue to disintegrate, there is a decline in person's cognitive abilities, memory, mood, spontaneity, and socializing behavior. A framework that sequentially interlinks all these phenomenons under one event is lacking. Accumulating evidence has indicated the role of insulin deficiency and insulin resistance as mediators of AD neurodegeneration. Herein, we reviewed the evidence stemming from the development of diabetes agent-induced AD animal model. Striking evidence has attributed loss of insulin receptor-bearing neurons to precede or accompany initial stage of AD. This state seems to progress with AD such that, in the terminal stages, it worsens and becomes global. Oxidative stress, tau hyperphosphorylation, APP-Aβ deposition, and impaired glucose and energy metabolism have all been linked to perturbation in insulin/IGF signaling. We conclude that AD could be referred to as "type 3 diabetes". Moreover, owing to common pathophysiology with diabetes common therapeutic regime could be effective for AD patients.
Keywords: Acetylcholine; Alzheimer’s disease; Anti-diabetics; Insulin signaling; Tau hyperphosphorylation; Type 3 diabetes.