LAUSR

HIGHLIGHTSGSK‐3&bgr; is involved in the physiological and pathological progress of DM and AD respectively.In DM, GSK‐3&bgr; is one of the key factors leading to insulin deficiency and insulin resistance.In AD, GSK‐3&bgr; plays an important role in hyperphosphorylation of microtubule‐associated protein tau.GSK‐3&bgr; as a potential link between DM and AD is reviewed.GSK‐3&bgr; as a link between DM and AD further supports that AD is regarded as Type 3 diabetes. ABSTRACT It is well known that Alzheimer's disease (AD) is closely related to diabetes mellitus (DM), and AD is also regarded as Type 3 diabetes (T3D). However, the exact link between AD and DM is still unclear. Recently, more and more evidence has shown that glycogen synthase kinase‐3&bgr; (GSK‐3&bgr;) may be the potential link between DM and AD. In DM, GSK‐3&bgr; is the crucial enzyme of glycogen synthesis, which plays a key role in regulating blood glucose. More importantly, GSK‐3&bgr; is one of the key factors leading to insulin deficiency and insulin resistance, and insulin resistance is an important hallmark of the occurrence and development of DM. In AD, GSK‐3&bgr; plays an important role in hyperphosphorylation of microtubule‐associated protein tau (tau), which is one of the pathological features in AD. GSK‐3&bgr; is one of the important kinases of tau phosphorylation and is involved in the insulin/phosphoinositide 3‐kinase/protein kinase B (insulin/PI3K/Akt) signaling pathway. Dysfunction of the insulin/PI3K/Akt signaling pathway, which regulates glucose metabolism in the brain, can lead to tau hyperphosphorylation in the brain of AD patents. Additionally, insulin resistance in DM may cause &bgr;‐amyloid (A&bgr;) deposition, which will be cleared by tau, but excessive phosphorylation of tau will further aggravate the neurotoxicity; then damage the brain and affect the cognitive function. GSK‐3&bgr; is considered as a common kinase in insulin signaling transduction and tau protein phosphorylation, so we have reasons to believe that GSK‐3&bgr; is a potential link between DM and AD.