Insulin-degrading enzyme (IDE) is also known to have Aβ-degrading properties, and hyperinsulinemia in diabetes mellitus competitively inhibits Aβ degradation (Craft and Watson, 2004; Qiu and Folstein, 2006). Indeed, IDE deficient mice demonstrate increased cerebral accumulation of endogenous Aβ with hyperinsulinemia and glucose intolerance (Farris et al., 2003), and IDE overexpression ameliorates Aβ pathology (Leissring et al., 2003), suggesting a link between insulin metabolism and Aβ degradation. However, clinical evidence is still lacking and further studies on the association of IDE with AD pathogenesis may uncover potential treatment targets in AD. Some researchers have labeled AD “type 3 diabetes” (de la Monte and Wands, 2008). If hyperinsulinemia is related to resistance of neuronal cells to insulin, impaired insulin signaling in neurons is thought to lead to neuronal disturbances. A clinical trial assessing intranasal insulin therapy in the treatment of AD and amnestic MCI is anticipated to further elaborate on the relationship between AD and insulin signaling (Craft et al., 2012).
