Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand; Centre for Brain Research, School of Medical Sciences, Faculty of Medical and Health Science, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand; Brain Research New Zealand, A Centre of Research Excellence, New Zealand.
Centre for Brain Research, School of Medical Sciences, Faculty of Medical and Health Science, University of Auckland, 85 Park Road, Grafton, Auckland 1023, New Zealand; Brain Research New Zealand, A Centre of Research Excellence, New Zealand; Department of Anatomy and Medical Imaging, Faculty of Medicine and Health Science, University of Auckland, New Zealand.
Psychoneuroendocrinology. 2021 May;127:105191. doi: 10.1016/j.psyneuen.2021.105191. Epub 2021 Mar 5.
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.
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.
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.
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.
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.
胰岛素样生长因子 (IGF) 结合蛋白 (IGFBP)-3 和环状甘氨酸-脯氨酸 (cGP) 调节与认知相关的循环 IGF-1 功能。IGF-1 功能与阿尔茨海默病 (AD) 之间的关联仍不确定。本研究评估了 IGFBPs 和 cGP 的变化及其对 AD 病例人类大脑中 IGF-1 生物利用度和功能的影响。
使用生物和数学分析，我们测量了 AD 病例（n=15）和对照组（n=15）下额额回和额中回中 IGF-1、IGFBPs 和 cGP 的总浓度、结合形式和游离形式。还分析了这些肽的总浓度变化与脑组织中总蛋白浓度之间的关系。
AD 病例中游离的生物可利用 IGF-1 较低，而结合的 cGP 和 IGFBP-3 较高。AD 病例中的总蛋白低于对照组，与对照组 cGP 浓度呈负相关，与 AD 病例 IGFBP-3 浓度呈负相关。
这些结果为 AD 大脑中 IGF-1 缺乏提供了直接证据，这是由于游离生物可利用 IGF-1 减少所致。结合 IGFBP-3 的增加损害了自分泌调节。结合 cGP 的增加是改善 AD 大脑中 IGF-1 生物利用度和功能的自分泌反应。
本研究中生成或分析的所有数据都包含在本文发表的文章中。如有需要，可向通讯作者索取本研究中额外分析的其他数据集。
