Decreased salivary lactoferrin levels are specific to Alzheimer's disease
Decreased salivary lactoferrin levels are specific to Alzheimer's disease
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DOI：
10.1016/j.ebiom.2020.102834
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发表时间：
2020-07-01
期刊：
影响因子：
11.1
通讯作者：
Carro, Eva
中科院分区：
文献类型：
--
作者：
Gonzalez-Sanchez, Marta;Bartolome, Fernando;Carro, Eva
背景：阿尔茨海默病(AD)脑内感染病原体的证据可能提示AD病理生理学中先天免疫系统的恶化。我们先前发现AD患者唾液乳铁蛋白(LF)水平降低，这是主要的抗菌蛋白之一。方法：为了评估唾液乳铁蛋白(LF)在AD诊断中的临床应用价值，我们利用淀粉样正电子发射断层扫描(PET)神经成像技术检测唾液LF与脑淀粉样β蛋白(Aβ)负荷之间的关系。在两个不同的横断面队列中，包括不同神经退行性疾病的患者。结果：队列1中唾液低频的诊断性能曲线下面积[AUC]为0.95(0.911-0.992)，用于区分前驱AD/AD组(PET+)与健康组，和0.97(0.924-1)对额颞叶痴呆(FTD)组。在队列2中，唾液LF在健康对照组和先兆AD组中的诊断性能也很好：AUC0.93(0.876-0.989)。唾液LF检测AD前驱症状和AD痴呆，与FTD相比，敏感性超过87%，特异性超过91%。我们的发现支持唾液Lf作为一种新的非侵入性和经济有效的AD生物标志物的可能用途。
Background: Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients.Methods: To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-beta (A beta) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders.Findings: The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0.95 (0.911-0.992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET+) versus healthy group, and 0.97 (0.924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0.93 (0.876-0.989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from FTD with over 87% sensitivity and 91% specificity.Interpretation: Salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker.