Background: Differential diagnosis of Alzheimer’s disease (AD) is a complex task due to the clinical similarity among neurodegenerative diseases. Previous studies showed the role of lipid peroxidation in early AD development. However, the clinical validation of potential specific biomarkers in minimally invasive samples constitutes a great challenge in early AD diagnosis. Methods: Plasma samples from participants classified into AD (n = 138), non-AD (including MCI and other dementias not due to AD) (n = 70) and healthy (n = 50) were analysed. Lipid peroxidation compounds (isoprostanes, isofurans, neuroprostanes, neurofurans) were determined by ultra-performance liquid chromatography coupled with tandem mass spectrometry. Statistical analysis for biomarkers’ clinical validation was based on Elastic Net. Results: A two-step diagnosis model was developed from plasma lipid peroxidation products to diagnose early AD specifically, and a bootstrap validated AUC of 0.74 was obtained. Conclusion: A promising AD differential diagnosis model was developed. It was clinically validated as a screening test. However, further external validation is required before clinical application.

中文翻译：

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血浆脂质过氧化生物标志物在阿尔茨海默氏病鉴别诊断中的临床效用。

背景：由于神经退行性疾病之间的临床相似性，对阿尔茨海默氏病（AD）进行鉴别诊断是一项复杂的任务。先前的研究表明脂质过氧化在AD早期发展中的作用。然而，微创样品中潜在特定生物标志物的临床验证对早期AD诊断构成了巨大挑战。方法：将血浆样本分为AD（n = 138），非AD（包括MCI和非AD引起的其他痴呆）（n = 70）和健康（n= 50）进行了分析。用超高效液相色谱-串联质谱法测定脂质过氧化化合物（异前列腺素，异呋喃，神经前列腺素，神经呋喃）。用于生物标志物临床验证的统计分析基于弹性网。结果：从血浆脂质过氧化产物建立了一个两步诊断模型，专门用于诊断早期AD，并且获得的bootstrap验证的AUC为0.74。结论：建立了有希望的AD鉴别诊断模型。临床上已将其验证为筛选测试。但是，在临床应用之前需要进一步的外部验证。