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泪液中的β-淀粉样肽:与脉络膜厚度相关的阿尔茨海默病早期诊断标志物

Beta-Amyloid Peptide in Tears: An Early Diagnostic Marker of Alzheimer's Disease Correlated with Choroidal Thickness.

机构信息

Department of Sense Organs, Sapienza University of Rome, 155, Viale del Policlinico, 00161 Rome, Italy.

Department of Human Neurosciences, Sapienza University of Rome, 00185 Rome, Italy.

出版信息

Int J Mol Sci. 2023 Jan 30;24(3):2590. doi: 10.3390/ijms24032590.

Abstract

We aimed to evaluate the diagnostic role of Alzheimer's disease (AD) biomarkers in tears as well as their association with retinal and choroidal microstructures. In a cross-sectional study, 35 subjects (age 71.7 ± 6.9 years) were included: 11 with prodromal AD (MCI), 10 with mild-to-moderate AD, and 14 healthy controls. The diagnosis of AD and MCI was confirmed according to a complete neuropsychological evaluation and PET or MRI imaging. After tear sample collection, β-amyloid peptide Aβ1-42 concentration was analyzed using ELISA, whereas C-terminal fragments of the amyloid precursor protein (APP-CTF) and phosphorylated tau (p-tau) were assessed by Western blot. Retinal layers and choroidal thickness (CT) were acquired by spectral-domain optical coherence tomography (SD-OCT). Aβ1-42 levels in tears were able to detect both MCI and AD patients with a specificity of 93% and a sensitivity of 81% (AUC = 0.91). Tear levels of Aβ1-42 were lower, both in the MCI ( < 0.01) and in the AD group ( < 0.001) when compared to healthy controls. Further, Aβ1-42 was correlated with psychometric scores ( < 0.001) and CT ( < 0.01). CT was thinner in the affected patients ( = 0.035). No differences were observed for APP-CTF and p-tau relative abundance in tears. Testing Aβ1-42 levels in tears seems to be a minimally invasive, cost-saving method for early detection and diagnosis of AD.

摘要

我们旨在评估阿尔茨海默病(AD)生物标志物在泪液中的诊断作用及其与视网膜和脉络膜微观结构的关系。在一项横断面研究中,纳入了 35 名受试者(年龄 71.7 ± 6.9 岁):11 名前驱性 AD(MCI)患者,10 名轻度至中度 AD 患者,和 14 名健康对照者。AD 和 MCI 的诊断是根据全面的神经心理学评估以及 PET 或 MRI 成像来确认的。收集泪样后,采用 ELISA 分析 β-淀粉样肽 Aβ1-42 浓度,而用 Western blot 评估淀粉样前体蛋白(APP)的 C 端片段(APP-CTF)和磷酸化 tau(p-tau)。通过光谱域光相干断层扫描(SD-OCT)获取视网膜层和脉络膜厚度(CT)。泪液中 Aβ1-42 水平能够以 93%的特异性和 81%的敏感性检测出 MCI 和 AD 患者(AUC = 0.91)。与健康对照组相比,MCI( < 0.01)和 AD 组( < 0.001)的泪液 Aβ1-42 水平均较低。此外,Aβ1-42 与心理测量评分( < 0.001)和 CT( < 0.01)相关。受影响患者的 CT 更薄( = 0.035)。在泪液中,APP-CTF 和 p-tau 的相对丰度无差异。检测泪液中的 Aβ1-42 水平似乎是一种微创、节省成本的方法,可用于 AD 的早期检测和诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d48e/9917300/dfb86b311d6b/ijms-24-02590-g001.jpg

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