大脑胰岛素抵抗和缺乏是阿尔茨海默病 (AD) 的一贯特征。胰岛素抵抗可以通过胰岛素受体（IR）的表面表达介导。 IR 的裂解产生可溶性 IR (sIR)。我们测量了来自两个队列的 AD 诊断谱中个体的脑脊液 (CSF) 中存在的 sIR 水平：西雅图 (n = 58) 和早期识别联盟阿尔茨海默病 - 魁北克 (CIMA-Q；n = 61)。我们使用人类细胞系进一步研究了脑细胞对 sIR 的贡献。AD 中脑脊液 sIR 水平没有统计学差异。在 CIMA-Q 队列中，CSF sIR 与淀粉样蛋白 β (Aβ)42 和 Aβ40 水平以及 CSF sIR 和认知显着相关。表达淀粉样前体蛋白“Swedish”突变的人类神经元产生显着更高的 sIR，并且人类星形胶质细胞也能够响应炎症和胰岛素刺激而释放 sIR。这些数据支持进一步研究 sIR 在 AD 中的产生和作用。脑脊液 (CSF) 可溶性胰岛素受体 (SIR) 水平与淀粉样蛋白 β (Aβ)42 和 Aβ40 呈正相关。脑脊液 sIR 水平与认知表现（蒙特利尔认知评估评分）呈负相关。人类脑脊液 sIR 水平在阿尔茨海默病诊断组中保持相似.来自具有“瑞典”突变（其中 Aβ42 增加）的人类神经元会产生更高水平的 sIR。人类星形胶质细胞也可以产生 sIR，并且肿瘤坏死因子 α 和胰岛素会刺激其产生。© 2024 作者。老年痴呆症

Brain insulin resistance and deficiency is a consistent feature of Alzheimer's disease (AD). Insulin resistance can be mediated by the surface expression of the insulin receptor (IR). Cleavage of the IR generates the soluble IR (sIR).We measured the levels of sIR present in cerebrospinal fluid (CSF) from individuals along the AD diagnostic spectrum from two cohorts: Seattle (n = 58) and the Consortium for the Early Identification of Alzheimer's Disease-Quebec (CIMA-Q; n = 61). We further investigated the brain cellular contribution for sIR using human cell lines.CSF sIR levels were not statistically different in AD. CSF sIR and amyloid beta (Aβ)42 and Aβ40 levels significantly correlated as well as CSF sIR and cognition in the CIMA-Q cohort. Human neurons expressing the amyloid precursor protein "Swedish" mutation generated significantly greater sIR and human astrocytes were also able to release sIR in response to both an inflammatory and insulin stimulus.These data support further investigation into the generation and role of sIR in AD.Cerebrospinal fluid (CSF) soluble insulin receptor (sIR) levels positively correlate with amyloid beta (Aβ)42 and Aβ40.CSF sIR levels negatively correlate with cognitive performance (Montreal Cognitive Assessment score).CSF sIR levels in humans remain similar across Alzheimer's disease diagnostic groups.Neurons derived from humans with the "Swedish" mutation in which Aβ42 is increased generate increased levels of sIR.Human astrocytes can also produce sIR and generation is stimulated by tumor necrosis factor α and insulin.© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.