背景:已经在脑脊液和血液中广泛研究了蛋白质生物标志物,用于检测神经退行性疾病,然而,临床上有用的诊断测试,以早期发现,症状前的阿尔茨海默病(AD)仍然难以捉摸。我们进行了这项研究来量化Aβ40,Aβ42,总Tau(t-Tau),高磷酸化Tau(ptau181),相对于血液,眼液中的神经胶质纤维酸性蛋白(GFAP)和神经丝轻链(NfL)。
方法:在这项横断面研究中,我们收集了玻璃体液,房水,眼病手术患者的泪液和血浆。通过数字免疫测定对所有6种生物标志物进行定量测量。进行Spearman和Bland-Altman相关性分析以评估眼液和血浆之间的水平一致性。
结果:79名成年人至少有一只眼睛接受了玻璃体切割术。79人中有77个玻璃体,67血,56泪液,和51个含水样品。在每个生物样本中对所有六个生物标志物进行了定量,除了泪液中的GFAP和NfL,由于样品体积较低。与血浆样品相比,所有六种生物标志物在玻璃体液中升高。T-Tau,水溶液中的ptau181,GFAP和NfL高于血浆中,泪液中t-Tau和ptau181的浓度高于血浆。血浆中Aβ40与泪液存在显著相关性(r=0.5;p=0.019),血浆和玻璃体中的t-Tau(r=0.4;p=0.004),血浆和玻璃体中的NfL(r=0.3;p=0.006)以及血浆和水溶液中的NfL(r=0.5;p=0.004)。相对于血浆,眼液中的Aβ42,ptau181和GFAP未发现显着关联。Bland-Altman分析显示房水在所有生物标志物中与血浆最接近。眼液中的生物标志物水平显示,t-Tau的玻璃体和房水之间存在统计学上的显着关联(r=0.5;p=0.001),GFAP(r=0.6;p<0.001)和NfL(r=0.7;p<0.001)。
结论:AD生物标志物在眼液中的检测量大于血浆中的检测量,并显示与血浆水平的相关性。未来的研究需要评估眼液生物标志物作为AD诊断和预后标志物的实用性。尤其是那些有眼病风险的人。
BACKGROUND: Protein biomarkers have been broadly investigated in cerebrospinal fluid and blood for the detection of neurodegenerative diseases, yet a clinically useful diagnostic test to detect early, pre-symptomatic Alzheimer\'s disease (AD) remains elusive. We conducted this study to quantify Aβ40, Aβ42, total Tau (t-Tau), hyperphosphorylated Tau (ptau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in eye fluids relative to blood.
METHODS: In this cross-sectional study we collected vitreous humor, aqueous humor, tear fluid and plasma in patients undergoing surgery for eye disease. All six biomarkers were quantitatively measured by digital immunoassay. Spearman and Bland-Altman correlation analyses were performed to assess the agreement of levels between ocular fluids and plasma.
RESULTS: Seventy-nine adults underwent pars-plana vitrectomy in at least one eye. Of the 79, there were 77 vitreous, 67 blood, 56 tear fluid, and 51 aqueous samples. All six biomarkers were quantified in each bio-sample, except GFAP and NfL in tear fluid due to low sample volume. All six biomarkers were elevated in vitreous humor compared to plasma samples. T-Tau, ptau181, GFAP and NfL were higher in aqueous than in plasma, and t-Tau and ptau181 concentrations were higher in tear fluid than in plasma. Significant correlations were found between Aβ40 in plasma and tears (r = 0.5; p = 0.019), t-Tau in plasma and vitreous (r = 0.4; p = 0.004), NfL in plasma and vitreous (r = 0.3; p = 0.006) and plasma and aqueous (r = 0.5; p = 0.004). No significant associations were found for Aβ42, ptau181 and GFAP among ocular fluids relative to plasma. Bland-Altman analysis showed aqueous humor had the closest agreement to plasma across all biomarkers. Biomarker levels in ocular fluids revealed statistically significant associations between vitreous and aqueous for t-Tau (r = 0.5; p = 0.001), GFAP (r = 0.6; p < 0.001) and NfL (r = 0.7; p < 0.001).
CONCLUSIONS: AD biomarkers are detectable in greater quantities in eye fluids than in plasma and show correlations with levels in plasma. Future studies are needed to assess the utility of ocular fluid biomarkers as diagnostic and prognostic markers for AD, especially in those at risk with eye disease.