The autocrine regulation of insulin-like growth factor-1 in human brain of Alzheimer's disease.

Abstract

<h4>Background</h4>Insulin-like growth factor (IGF) binding protein (IGFBP)-3 and cyclic Glycine-Proline (cGP) regulate circulating IGF-1 function that is associated with cognition. The association between IGF-1 function and Alzheimer's disease (AD) remains inconclusive. This study evaluated the changes of IGFBPs and cGP, and their effects on the bioavailability and function of IGF-1 in human brain of AD cases.<h4>Methods</h4>Using biological and mathematic analysis we measured the concentrations of total, bound and unbound forms of IGF-1, IGFBPs and cGP in the inferior-frontal gyrus and middle-frontal gyrus of human AD (n = 15) and control cases (n = 15). The association between the changes of total concentration of these peptides and total protein concentration in brain tissues were also analyzed.<h4>Results</h4>The unbound bioavailable IGF-1 was lower whereas the bound cGP and IGFBP-3 were higher in AD than the control cases. Total protein that was lower in AD than control cases, was negatively associated with cGP concentration of control cases and with IGFBP-3 concentration of AD cases.<h4>Conclusions</h4>The results provide direct evidence for IGF-1 deficiency in AD brain due to lower bioavailable IGF-1. The increase of bound IGFBP-3 impaired autocrine regulation. The increase of bound cGP is an autocrine response to improve the bioavailability and function of IGF-1 in AD brain.<h4>Availability of data and material</h4>All data generated or analysed during this study are included in this published article. Additional datasets analysed during the current study available from the corresponding author on reasonable request.