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阿尔茨海默病患者脑脊液和皮质组织中的致密核心囊泡标志物。

Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer's disease.

机构信息

Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, 08028, Barcelona, Spain.

Institute of Neurosciences, University of Barcelona, 08028, Barcelona, Spain.

出版信息

Transl Neurodegener. 2021 Sep 26;10(1):37. doi: 10.1186/s40035-021-00263-0.

DOI:10.1186/s40035-021-00263-0
PMID:34565482
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8466657/
Abstract

BACKGROUND

New fluid biomarkers for Alzheimer's disease (AD) that reveal synaptic and neural network dysfunctions are needed for clinical practice and therapeutic trial design. Dense core vesicle (DCV) cargos are promising cerebrospinal fluid (CSF) indicators of synaptic failure in AD patients. However, their value as biomarkers has not yet been determined.

METHODS

Immunoassays were performed to analyze the secretory proteins prohormone convertases PC1/3 and PC2, carboxypeptidase E (CPE), secretogranins SgIII and SgII, and Cystatin C in the cerebral cortex (n = 45, provided by Bellvitge University Hospital) and CSF samples (n = 66, provided by The Sant Pau Initiative on Neurodegeneration cohort) from AD patients (n = 56) and age-matched controls (n = 55).

RESULTS

In AD tissues, most DCV proteins were aberrantly accumulated in dystrophic neurites and activated astrocytes, whereas PC1/3, PC2 and CPE were also specifically accumulated in hippocampal granulovacuolar degeneration bodies. AD individuals displayed an overall decline of secretory proteins in the CSF. Interestingly, in AD patients, the CSF levels of prohormone convertases strongly correlated inversely with those of neurodegeneration markers and directly with cognitive impairment status.

CONCLUSIONS

These results demonstrate marked alterations of neuronal-specific prohormone convertases in CSF and cortical tissues of AD patients. The neuronal DCV cargos are biomarker candidates for synaptic dysfunction and neurodegeneration in AD.

摘要

背景

需要新的阿尔茨海默病（AD）液体生物标志物来揭示突触和神经网络功能障碍，以便于临床实践和治疗试验设计。致密核心囊泡（DCV）货物是 AD 患者突触衰竭的有前途的脑脊液（CSF）指标。然而，它们作为生物标志物的价值尚未确定。

方法

进行免疫测定以分析前激素转化酶 PC1/3 和 PC2、羧肽酶 E（CPE）、分泌颗粒 SgIII 和 SgII 以及胱抑素 C 在大脑皮层（n=45，由 Bellvitge 大学医院提供）和 CSF 样本（n=66，由 Sant Pau 神经退行性变倡议队列提供）中的含量，这些样本来自 AD 患者（n=56）和年龄匹配的对照组（n=55）。

结果

在 AD 组织中，大多数 DCV 蛋白在萎缩的神经突和激活的星形胶质细胞中异常积累，而 PC1/3、PC2 和 CPE 也特异性地积累在海马粒空泡变性体中。AD 个体的 CSF 中分泌蛋白总体下降。有趣的是，在 AD 患者中，前激素转化酶的 CSF 水平与神经退行性标志物呈负相关，与认知障碍状况呈正相关。

结论

这些结果表明 AD 患者 CSF 和皮质组织中神经元特异性前激素转化酶发生明显改变。神经元 DCV 货物是 AD 中突触功能障碍和神经退行性变的候选生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/cba135d3e9df/40035_2021_263_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/0fb9779c4043/40035_2021_263_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/50496668ff68/40035_2021_263_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/9b0a7c42c640/40035_2021_263_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/15ccf5c3333f/40035_2021_263_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/2c241a81bf13/40035_2021_263_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/69c2279a50d4/40035_2021_263_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/cba135d3e9df/40035_2021_263_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/0fb9779c4043/40035_2021_263_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/50496668ff68/40035_2021_263_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/9b0a7c42c640/40035_2021_263_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/15ccf5c3333f/40035_2021_263_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/2c241a81bf13/40035_2021_263_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/69c2279a50d4/40035_2021_263_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2741/8466657/cba135d3e9df/40035_2021_263_Fig7_HTML.jpg

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