Cerebrospinal fluid shotgun proteomics identifies distinct proteomic patterns in cerebral amyloid angiopathy rodent models and human patients.
Cerebrospinal fluid shotgun proteomics identifies distinct proteomic patterns in cerebral amyloid angiopathy rodent models and human patients.
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DOI：
10.1186/s40478-023-01698-4
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发表时间：
2024-01-08
影响因子：
7.1
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中科院分区：
文献类型：
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脑淀粉样血管病（CAA）是一种小血管疾病，其特征是淀粉样β蛋白在脑血管系统中进行性沉积，引起包括认知障碍和脑出血在内的症状。由于其可及性和同质的疾病表型，动物模型是研究CAA等疾病的有利平台。CAA大鼠模型（例如rTg-DI）和CAA患者的非靶向蛋白质组学研究为鉴定CAA的新生物标志物提供了机会。我们对rTg-DI大鼠和野生型（WT）同窝仔的脑脊液进行了非靶向的、数据独立的采集蛋白质组鸟枪分析。分别在3个月（n = 6/10）、6个月（n = 8/8）和12个月（n = 10/10）时分析啮齿动物的rTg-DI和WT。对于人类，对散发性CAA患者（sCAA）和对照参与者（n = 39/28）的CSF进行蛋白质组学分析。与野生型大鼠相比，我们显示了rTg-DI大鼠中差异表达（主要是增加）蛋白质的重复模式，特别是组织蛋白酶蛋白家族（CTSB，CTSD，CTSS）及其主要抑制剂（CST 3）的蛋白酶。在sCAA患者中，发现与对照相比，突触蛋白（例如包括VGF、NPTX 1、NRXN 2）和颗粒蛋白家族的几个成员（SCG 1、SCG 2、SCG 3、SCG 5）的水平降低。此外，与对照相比，SERPIN蛋白家族的几种丝氨酸蛋白酶抑制剂（包括SERPINA 3、SERPINC 1和SERPING 1）差异表达。15种蛋白质在rTg-DI大鼠和sCAA患者中均显著改变，包括（除其他外）SCG 5和SERPING 1。这些结果鉴定了可能参与CAA病理学中所涉及的病理生理过程或受其影响的特定蛋白质组，例如rTg-DI大鼠模型和sCAA患者的蛋白酶和突触功能，并且可以作为sCAA的候选生物标志物。在线版本包含补充材料，可通过10.1186/s40478-023-01698-4获得。
Cerebral amyloid angiopathy (CAA) is a form of small vessel disease characterised by the progressive deposition of amyloid β protein in the cerebral vasculature, inducing symptoms including cognitive impairment and cerebral haemorrhages. Due to their accessibility and homogeneous disease phenotypes, animal models are advantageous platforms to study diseases like CAA. Untargeted proteomics studies of CAA rat models (e.g. rTg-DI) and CAA patients provide opportunities for the identification of novel biomarkers of CAA. We performed untargeted, data-independent acquisition proteomic shotgun analyses on the cerebrospinal fluid of rTg-DI rats and wild-type (WT) littermates. Rodents were analysed at 3 months (n = 6/10), 6 months (n = 8/8), and 12 months (n = 10/10) for rTg-DI and WT respectively. For humans, proteomic analyses were performed on CSF of sporadic CAA patients (sCAA) and control participants (n = 39/28). We show recurring patterns of differentially expressed (mostly increased) proteins in the rTg-DI rats compared to wild type rats, especially of proteases of the cathepsin protein family (CTSB, CTSD, CTSS), and their main inhibitor (CST3). In sCAA patients, decreased levels of synaptic proteins (e.g. including VGF, NPTX1, NRXN2) and several members of the granin family (SCG1, SCG2, SCG3, SCG5) compared to controls were discovered. Additionally, several serine protease inhibitors of the SERPIN protein family (including SERPINA3, SERPINC1 and SERPING1) were differentially expressed compared to controls. Fifteen proteins were significantly altered in both rTg-DI rats and sCAA patients, including (amongst others) SCG5 and SERPING1. These results identify specific groups of proteins likely involved in, or affected by, pathophysiological processes involved in CAA pathology such as protease and synapse function of rTg-DI rat models and sCAA patients, and may serve as candidate biomarkers for sCAA. The online version contains supplementary material available at 10.1186/s40478-023-01698-4.
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DOI：
10.1074/jbc.m112.417071
发表时间：
2013-01-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Helwig M;Hoshino A;Berridge C;Lee SN;Lorenzen N;Otzen DE;Eriksen JL;Lindberg I
通讯作者：
Lindberg I
生产阿尔茨海默氏病的β-淀粉样蛋白肽的替代途径。
影响因子：
3.7
作者：
Hook V;Schechter I;Demuth HU;Hook G
通讯作者：
Hook G
影响因子：
4.7
作者：
Schrader JM;Xu F;Van Nostrand WE
通讯作者：
Van Nostrand WE
影响因子：
29
作者：
Charidimou A;Martinez-Ramirez S;Reijmer YD;Oliveira-Filho J;Lauer A;Roongpiboonsopit D;Frosch M;Vashkevich A;Ayres A;Rosand J;Gurol ME;Greenberg SM;Viswanathan A
通讯作者：
Viswanathan A
DOI：
10.1016/j.cccb.2022.100133
发表时间：
2022
期刊：
Cerebral circulation - cognition and behavior
影响因子：
--
作者：
通讯作者：
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