背景:眼病患者发生神经退行性疾病的风险增加。可以在眼睛中测量神经变性蛋白;然而,眼液中生物标志物水平与神经病理学诊断之间的相关性尚未建立。
目的:这项探索性研究,回顾性研究检查了41只尸检眼睛和脑组织的玻璃体液,并进行了阿尔茨海默病的神经病理学诊断(AD,n=7),慢性创伤性脑病(CTE,n=15),AD+CTE(n=10),并且没有明显的神经病理学(对照,n=9)。
方法:蛋白质生物标志物,即β淀粉样蛋白(Aβ40,42),Totaltau(ttau),磷酸化tau(pTau181,231),神经丝轻链(NfL),和eotaxin-1通过免疫测定进行定量测定。非参数检验用于比较组间的玻璃体生物标志物水平。使用Spearman等级相关测试来关联玻璃体和皮质组织中的生物标志物水平。显著性水平设定为α=0.10。
结果:在成对比较中,与对照组相比,AD和CTE组的tTau水平显着增加(两者均为p=0.08),以及AD与ADCTE组和CTE与ADCTE组(两者均为p=0.049)。玻璃体NfL水平在低CTE(I/II期)与无CTE(p=0.096)和低CTE与高CTE阶段(p=0.03)显着增加。pTau231(p=0.02,r=0.38)和t-Tau(p=0.04,r=-0.34)的玻璃体和皮质组织水平显着相关。
结论:死后玻璃体液生物标志物水平与相应大脑中的AD和CTE病理显著相关,而玻璃体NfL与CTE分期相关。这项探索性研究表明,玻璃体液中的生物标志物可以作为神经病理学疾病的替代。
Patients with eye disease have an increased risk for developing neurodegenerative disease. Neurodegenerative proteins can be measured in the eye; however, correlations between biomarker levels in eye fluid and neuropathological diagnoses have not been established.
This exploratory, retrospective study examined vitreous humor from 41 postmortem eyes and brain tissue with neuropathological diagnoses of Alzheimer\'s disease (AD, n = 7), chronic traumatic encephalopathy (CTE, n = 15), both AD + CTE (n = 10), and without significant neuropathology (controls, n = 9).
Protein biomarkers i.e., amyloid-β (Aβ40,42), total tau (tTau), phosphorylated tau (pTau181,231), neurofilament light chain (NfL), and eotaxin-1 were quantitatively measured by immunoassay. Non-parametric tests were used to compare vitreous biomarker levels between groups. Spearman\'s rank correlation tests were used to correlate biomarker levels in vitreous and cortical tissue. The level of significance was set to α= 0.10.
In pairwise comparisons, tTau levels were significantly increased in AD and CTE groups versus controls (p = 0.08 for both) as well as AD versus AD+CTE group and CTE versus AD+CTE group (p = 0.049 for both). Vitreous NfL levels were significantly increased in low CTE (Stage I/II) versus no CTE (p = 0.096) and in low CTE versus high CTE stage (p = 0.03). Vitreous and cortical tissue levels of pTau 231 (p = 0.02, r = 0.38) and t-Tau (p = 0.04, r = -0.34) were significantly correlated.
The postmortem vitreous humor biomarker levels significantly correlate with AD and CTE pathology in corresponding brains, while vitreous NfL was correlated with the CTE staging. This exploratory study indicates that biomarkers in the vitreous humor may serve as a proxy for neuropathological disease.