Associations of Cerebrospinal Fluid Orexin-A, Alzheimer Disease Biomarkers, and Cognitive Performance

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY Annals of Clinical and Translational Neurology Pub Date : 2025-02-17 DOI:10.1002/acn3.70009

Ruijin Lu, Krish Shah, Cristina D. Toedebusch, Ashley Hess, Rachel Richardson, Emmanuel Mignot, Suzanne E. Schindler, Tammie L. S. Benzinger, Shaney Flores, Jason Hassenstab, Chengjie Xiong, John C. Morris, David M. Holtzman, Brendan P. Lucey

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Abstract

Objective

Cerebrospinal fluid (CSF) orexin-A has been suggested to be a biomarker of Alzheimer disease (AD). In both cognitively unimpaired healthy older adults and individuals with symptomatic AD, CSF orexin-A is positively associated with CSF Aβ42, p-tau181, and total tau (t-tau) concentrations. However, a recent systematic review and meta-analysis did not support differences in orexin-A between AD and controls. In this study, we tested the association between CSF orexin-A concentrations, AD biomarkers, and cognitive performance in older adults with and without symptomatic AD.

Methods

Two hundred and seventy community-dwelling older adults underwent standardized cognitive assessments, sleep monitoring with a single-channel electroencephalography test, one night of home sleep apnea testing, biofluid and imaging AD biomarker measurement within 1 year of sleep monitoring, and APOE genotyping. Plasma and CSF AD biomarkers were measured by immunoassay or mass spectrometry. CSF orexin-A was measured by radioimmunoassay.

Results

CSF orexin-A levels did not differ by amyloid positivity, cognitive status, or AD stage. However, CSF AD biomarkers (Aβ40, Aβ42, and t-tau) were positively associated with CSF orexin-A levels even after correction for multiple comparisons. CSF orexin-A was not associated with any measure of cognitive performance.

Interpretation

This study showed that CSF orexin-A is associated with multiple CSF AD biomarkers, but not with AD pathology or cognitive performance. We hypothesize that this is due to similar mechanisms of production/release of these proteins with sleep–wake activity. Future studies measuring other forms of orexin peptides, such as orexin-B, may provide evidence for orexin as a marker for AD.

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脑脊液食欲素- a、阿尔茨海默病生物标志物与认知表现的关系

目的：脑脊液（CSF）食欲素- a已被认为是阿尔茨海默病（AD）的生物标志物。在认知功能未受损的健康老年人和有症状的AD患者中，CSF orexin-A与CSF Aβ42、p-tau181和总tau （t-tau）浓度呈正相关。然而，最近的一项系统综述和荟萃分析并未支持AD和对照组之间食欲素a的差异。在这项研究中，我们测试了脑脊液食欲素- a浓度、AD生物标志物和有和无症状AD的老年人认知能力之间的关系。方法：270名居住在社区的老年人接受了标准化的认知评估、单通道脑电图睡眠监测、一晚家庭睡眠呼吸暂停测试、1年内睡眠监测中的生物体液和成像AD生物标志物测量以及APOE基因分型。采用免疫分析法或质谱法测定血浆和脑脊液AD生物标志物。放射免疫法测定脑脊液促食欲素a。结果：脑脊液食欲素- a水平与淀粉样蛋白阳性、认知状态或AD分期无关。然而，脑脊液AD生物标志物（Aβ40、Aβ42和t-tau）与脑脊液食欲素- a水平呈正相关，即使经过多次比较校正后也是如此。脑脊液食欲素- a与认知能力的任何测量都无关。该研究表明，CSF orexin-A与多种CSF AD生物标志物相关，但与AD病理或认知表现无关。我们假设这是由于这些蛋白质的产生/释放机制与睡眠-觉醒活动相似。未来的研究测量其他形式的食欲素肽，如食欲素- b，可能会为食欲素作为AD的标志物提供证据。

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来源期刊

Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)

CiteScore

9.10

自引率

1.90%

发文量

218

审稿时长

8 weeks

期刊介绍： Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.