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帕金森病患者脑脊液中载脂蛋白 E、载脂蛋白 J 和脂蛋白结合的α-突触核蛋白水平升高 - 在 BioFIND 队列中的验证。

Elevated ApoE, ApoJ and lipoprotein-bound α-synuclein levels in cerebrospinal fluid from Parkinson's disease patients - Validation in the BioFIND cohort.

机构信息

Laboratory of Translational Neuropharmacology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Laboratory of Translational Neuropharmacology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

出版信息

Parkinsonism Relat Disord. 2023 Nov;116:105765. doi: 10.1016/j.parkreldis.2023.105765. Epub 2023 Jul 12.

Abstract

BACKGROUND

The progressive accumulation, aggregation, and spread of α-synuclein (aSN) are common hallmarks of Parkinson's disease (PD) pathology. The genotype of apolipoprotein E (ApoE) influences PD progression. Recently we found that aSN co-localize with apolipoproteins on lipoprotein vesicles. We reported an increased level of ApoE, ApoJ and lipoprotein-bound aSN in CSF from early PD patients compared to matched controls. We also found reduced plasma ApoAI in PD patients.

OBJECTIVE

In this study, we used the same approach on the BioFIND cohort to validate our previous results and extended the studies to examine correlations with ApoE genotype, demographic variables, clinical symptoms and other biochemical findings reported in the BioFIND cohort.

METHODS

For the assessment, we used Western-Blot (WB) technique for apolipoproteins measurements in CSF and plasma from PD patients and healthy controls. Further, for measurement of aSN bound to lipoproteins, we combined immunodepletion with the enzyme-linked immunosorbent assay (ELISA).

RESULTS

Levels of ApoE, ApoJ and lipoprotein bound aSN were significantly increased in CSF from PD patients compared to controls. We also observed decreased levels of ApoAI and ApoJ in plasma from PD patients compared to controls.

CONCLUSIONS

Concluding, the present data validated our previous findings. Altered lipoproteins appear to be important in early PD pathology and may be involved in mechanisms underlying aSN cell-to-cell transfer in the nervous system and be developed in algorithms for early diagnosis of PD.

摘要

背景

α-突触核蛋白(aSN)的渐进性积累、聚集和扩散是帕金森病(PD)病理学的共同特征。载脂蛋白 E(ApoE)的基因型影响 PD 的进展。最近,我们发现 aSN 与脂蛋白囊泡上的载脂蛋白共定位。我们报道与匹配的对照相比,早期 PD 患者脑脊液中的 ApoE、ApoJ 和脂蛋白结合的 aSN 水平升高。我们还发现 PD 患者血浆中的 ApoAI 降低。

目的

在本研究中,我们使用相同的方法对 BioFIND 队列进行验证,以验证我们之前的结果,并扩展研究以检查与 ApoE 基因型、人口统计学变量、临床症状和 BioFIND 队列中报告的其他生化发现的相关性。

方法

对于评估,我们使用 Western-Blot(WB)技术测量 PD 患者和健康对照的 CSF 和血浆中的载脂蛋白。此外,为了测量与脂蛋白结合的 aSN,我们将免疫沉淀与酶联免疫吸附测定(ELISA)相结合。

结果

与对照组相比,PD 患者脑脊液中的 ApoE、ApoJ 和脂蛋白结合的 aSN 水平显著升高。我们还观察到与对照组相比,PD 患者血浆中的 ApoAI 和 ApoJ 水平降低。

结论

总之,目前的数据验证了我们之前的发现。改变的脂蛋白在早期 PD 病理学中似乎很重要,并且可能与 aSN 细胞间转移的机制有关,并可能在 PD 的早期诊断算法中得到发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1b0/11140586/301162d7d1a6/nihms-1995748-f0001.jpg

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