与血浆相比,眼球不同腔室中的神经退行性病变生物标记物:一项协议验证研究。

IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Alzheimer's Research & Therapy Pub Date : 2024-08-26 DOI:10.1186/s13195-024-01556-y
Konstantina Sampani, Steven Ness, Fatima Tuz-Zahra, Nurgul Aytan, Elizabeth E Spurlock, Sreevardhan Alluri, Xuejing Chen, Nicole H Siegel, Michael L Alosco, Weiming Xia, Yorghos Tripodis, Thor D Stein, Manju L Subramanian
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引用次数: 0

摘要

背景:人们已经对脑脊液和血液中的蛋白质生物标志物进行了广泛研究,以检测神经退行性疾病,但检测早期、症状前阿尔茨海默病(AD)的临床有用诊断测试仍未出现。我们进行了这项研究,对眼液中的 Aβ40、Aβ42、总 Tau(t-Tau)、高磷酸化 Tau(ptau181)、神经纤维酸性蛋白(GFAP)和神经丝轻链(NfL)进行量化:在这项横断面研究中,我们收集了眼疾手术患者的玻璃体、房水、泪液和血浆。所有六种生物标志物均采用数字免疫测定法进行定量测定。通过斯皮尔曼和布兰德-阿尔特曼相关分析来评估眼液和血浆之间的水平一致性:79名成人至少有一只眼睛接受了眼旁玻璃体切除术。在这 79 例样本中,有 77 例玻璃体样本、67 例血液样本、56 例泪液样本和 51 例水样本。除了泪液样本中的 GFAP 和 NfL 因样本量较少而无法定量外,其他六个生物标记物均在每个生物样本中进行了定量。与血浆样本相比,玻璃体样本中的六种生物标记物均有所升高。水样中T-Tau、ptau181、GFAP和NfL的浓度高于血浆,泪液中t-Tau和ptau181的浓度高于血浆。血浆和泪液中的 Aβ40(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)以及血浆和水液(r = 0.5;p = 0.004)之间存在显著相关性。与血浆相比,眼液中的 Aβ42、ptau181 和 GFAP 没有发现明显的关联。Bland-Altman分析显示,在所有生物标记物中,眼液与血浆的一致性最接近。眼液中的生物标记物水平显示,玻璃体和水液中的t-Tau(r = 0.5; p = 0.001)、GFAP(r = 0.6; p 结论:玻璃体和水液中的生物标记物水平与血浆中的t-Tau(r = 0.5; p = 0.001)和GFAP(r = 0.6; p = 0.001)有统计学意义:眼液中AD生物标志物的检测量高于血浆,并与血浆中的水平存在相关性。今后还需要进行研究,以评估眼液生物标志物作为 AD 诊断和预后标志物的效用,尤其是对眼疾高危人群的效用。
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Neurodegenerative biomarkers in different chambers of the eye relative to plasma: an agreement validation study.

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).

Conclusion: 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.

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来源期刊
Alzheimer's Research & Therapy
Alzheimer's Research & Therapy 医学-神经病学
CiteScore
13.10
自引率
3.30%
发文量
172
审稿时长
>12 weeks
期刊介绍: Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.
期刊最新文献
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