背景:帕金森病的症状主要表现在显著且不可逆的神经病理学之后。因此,需要在显著的神经元变性发生之前鉴定能够提供疾病指征的生物标志物。
目的:评估帕金森病患者和健康对照者泪液中α-突触核蛋白浓度的差异。
方法:PubMed,Scopus,和WebofScience。最后一次数据库搜索是在2023年12月20日。
方法:在人类中进行的主要前瞻性研究,测量泪液中α-突触核蛋白的水平,并使用平均值或中位数报告临床结果。
方法:帕金森病患者和健康对照者。
方法:使用纽卡斯尔-渥太华量表评估偏倚风险。I2统计量用于估计异质性。结果测量是泪液总量和寡聚α-突触核蛋白的差异。平均差异(MD)用于评估结果。根据建议评估和开发与评估(GRADE)系统对证据的确定性进行评级。
结果:来自五项研究的三百二十七名帕金森氏病和312名健康对照受试者以及来自两项研究的177名帕金森氏病和166名健康对照受试者被纳入总α-突触核蛋白水平和寡聚α-突触核蛋白水平分析。分别。帕金森病和健康对照之间的总α-突触核蛋白水平没有差异(MD=0.02ng/mL[95%置信区间{CI}:0.00至0.05ng/mL;I2=90%;Z=1.79;p=0.07;研究数量=5;GRADE评级=非常低])。根据疾病持续时间对数据进行分层,与健康对照组相比,帕金森病病程≥7年的受试者的总α-突触核蛋白较高(MD=0.04ng/mL[95%CI:0.03至0.05ng/mL;I2=0%;Z=8.24,p<0.00001;研究数量=2;GRADE等级=低]),但两组之间没有差异(MD=-0.12ng/mL;GRADE等级:-0.38至0.93%=0.15/mL;与对照组相比,帕金森病患者的低聚α-突触核蛋白水平较高(MD=6.50ng/mL[95%CI:2.79至10.20ng/mL;I2=94%;Z=3.44;p=0.0006;研究数量=2;GRADE评级=非常低])。
结论:研究之间的高度异质性。由于研究数量有限,无法探索异质性的潜在来源。
结论:泪液α-突触核蛋白有可能成为帕金森病的非侵入性生物标志物。研究是,然而,需要增加生物标志物的确定性,并确定泪液中蛋白质的变化如何与帕金森病的进展和严重程度相关。
BACKGROUND: Parkinson\'s disease symptoms mostly manifest after significant and irreversible neuropathology. Hence, there is a need to identify biomarkers that can provide indications of disease before significant neuronal degeneration occurs.
OBJECTIVE: To estimate the difference in the concentration of α-synuclein protein in
tears between individuals with Parkinson\'s disease and healthy controls.
METHODS: PubMed, Scopus, and Web of Science. The last database search was on December 20, 2023.
METHODS: Primary prospective studies in humans measuring the level of α-synuclein in
tears and clinical outcomes reported using mean or median.
METHODS: Individuals with Parkinson\'s disease and healthy controls.
METHODS: The risk of bias was assessed using the Newcastle-Ottawa Scale. The I2 statistic was used to estimate heterogeneity. The outcome measure was the difference in tear total and oligomeric α-synuclein. Mean difference (MD) was used to assess the outcome. The certainty of evidence was rated following the Grading of Recommendations Assessment and Development and Evaluation (GRADE) system.
RESULTS: Three hundred twenty-seven Parkinson\'s disease and 312 healthy control subjects from five studies and 177 Parkinson\'s disease and 166 healthy control subjects from two studies were included in total α-synuclein levels and oligomeric α-synuclein levels analysis, respectively. Total α-synuclein level was not different between Parkinson\'s disease and healthy controls (MD = 0.02 ng/mL [95% confidence interval {CI}: 0.00 to 0.05 ng/mL; I2 = 90%; Z = 1.79; p=0.07; number of studies = 5; GRADE rating = very low]). Stratifying the data based on disease duration, total α-synuclein was higher in subjects with Parkinson\'s disease duration ≥7 years compared with healthy controls (MD = 0.04 ng/mL [95% CI: 0.03 to 0.05 ng/mL; I2 = 0%; Z = 8.24, p<0.00001; number of studies = 2; GRADE rating = low]) but not different between the two groups (MD = -0.12 ng/mL (95% CI: -0.38 to 0.15 ng/mL; I2 = 93%; Z = 0.84, p=0.40; number of studies = 3; GRADE rating = very low]). Oligomeric α-synuclein level was higher in Parkinson\'s disease compared with controls (MD = 6.50 ng/mL [95% CI: 2.79 to 10.20 ng/mL; I2 = 94%; Z = 3.44; p=0.0006; number of studies = 2; GRADE rating = very low]).
CONCLUSIONS: High heterogeneity between studies. Potential sources of heterogeneity could not be explored due to the limited number of studies.
CONCLUSIONS: Tear α-synuclein has the potential to be a noninvasive biomarker for Parkinson\'s disease. Studies are, however, needed to increase certainty in the biomarker and establish how the protein\'s changes in
tears correlate with Parkinson\'s disease progression and severity.