Hyperinsulinemia and risk of Alzheimer disease

Abstract

Hyperinsulinemia is associated with a higher risk of AD and decline in memory.

Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease

“…6 Furthermore, insulin resistance is implicated as an AD risk factor 26,27 and there are links between hyperinsulinemia, AD and APOE e4. 12 In fact, we observed a mild elevation in baseline plasma insulin values in this ITT population, which may indicate the presence of insulin resistance. However, the apparent interaction we observed was difficult to interpret owing to an inverted response in the 4 mg RSG APOE e4-positive treatment group and will be investigated in future studies.…”

“…11 Insulin has involvement in normal memory function and disorders in peripheral insulin metabolism, such as insulin resistance and hyperinsulinemia, may have a negative influence on memory, as well as increase the risk of developing AD. [12][13][14] Peroxisome proliferator-activated receptor g (PPARg) mediates the transcriptional enhancement of a number of genes encoding proteins that regulate lipid metabolism, suggesting a pivotal role in the adipogenic signaling cascade and lipid homeostasis. 15 Rosiglitazone (RSG), a PPARg agonist and an approved antidiabetic pharmacotherapy, is an insulinsensitizing agent that allows the body to use endogenous insulin more efficiently, maintain normal physiological feedback mechanisms 16,17 and produce anti-inflammatory actions.…”

Metal ions affect insulin-degrading enzyme activity

“…It is also interesting to outline that if we compare these parameters with those obtained for the amyloid peptides Aβ [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] and Aβ [16][17][18][19][20][21][22][23][24][25][26][27][28] several similarities and some differences emerge [54]. In particular, the overall proteolytic activity toward the main cleavage sites (i.e., Phe 24 [16][17][18][19][20][21][22][23][24][25][26][27][28] ) is somewhat higher in the case of the B20-30 peptide due to a slightly more efficient cleavage rate-limiting step (see Table 2), whereas the substrate affinity of B20-30 appears intermediate between that of Aβ [1][2][3]…”

“…Many in vitro and in vivo studies have shown that IDE is able to degrade several different substrates besides insulin [4], and amyloid-β peptides (Aβs) among the others [5]. For this reason, as hyperinsulinemia is associated with a high risk of Alzheimer's disease (AD) [6,7], IDE could play a critical role in the mechanism associating hyperinsulinemia and type 2 diabetes (DM2) with AD. Despite the evident role of IDE in various diseases, relatively little is known about its physiological functions and for this reason the control of its activity has been recently targeted as a viable approach in the study of diseases such as AD and insulindependent diabetes [8][9][10].…”

Uncontrolled diabetes increases the risk of Alzheimer’s disease: a population-based cohort study

“…The global prevalent dementia cases are approximately 29 million, with 4.6 million new cases every year [3]. Population-based longitudinal studies have consistently reported that diabetes is associated with an increased risk of dementia, although the relationship between diabetes and Alzheimer-type dementia is less clear [4][5][6][7][8][9][10][11][12][13][14][15][16]. Some of these studies found that the association is due to an increased incidence of vascular dementia (VaD) [6,8,16] or of Alzheimer's disease [4,14], and only one study reported an increased incidence of both VaD and Alzheimer's disease [7].…”