Identification of Clinically Relevant Brain Endothelial Cell Biomarkers in Plasma

医学 白质 神经血管束 病变 高强度 病理 腔隙性中风 磁共振成像 内科学 缺血性中风 缺血 放射科
作者
Jenifer Cordon,Michael R. Duggan,Gabriela Gómez,Krishna A. Pucha,Zhongsheng Peng,Heather E. Dark,Christos Davatzikos,Güray Erus,Alexandria Lewis,Abhay Moghekar,Julián Candia,Luigi Ferrucci,Dimitrios Kapogiannis,Keenan A. Walker
出处
期刊:Stroke [Lippincott Williams & Wilkins]
卷期号:54 (11): 2853-2863 被引量:6
标识
DOI:10.1161/strokeaha.123.043908
摘要

BACKGROUND: Proteins expressed by brain endothelial cells (BECs), the primary cell type of the blood-brain barrier, may serve as sensitive plasma biomarkers for neurological and neurovascular conditions, including cerebral small vessel disease. METHODS: Using data from the BLSA (Baltimore Longitudinal Study of Aging; n=886; 2009–2020), BEC-enriched proteins were identified among 7268 plasma proteins (measured with SomaScanv4.1) using an automated annotation algorithm that filtered endothelial cell transcripts followed by cross-referencing with BEC-specific transcripts reported in single-cell RNA-sequencing studies. To identify BEC-enriched proteins in plasma most relevant to the maintenance of neurological and neurovascular health, we selected proteins significantly associated with 3T magnetic resonance imaging–defined white matter lesion volumes. We then examined how these candidate BEC biomarkers related to white matter lesion volumes, cerebral microhemorrhages, and lacunar infarcts in the ARIC study (Atherosclerosis Risk in Communities; US multisite; 1990–2017). Finally, we determined whether these candidate BEC biomarkers, when measured during midlife, were related to dementia risk over a 25-year follow-up period. RESULTS: Of the 28 proteins identified as BEC-enriched, 4 were significantly associated with white matter lesion volumes (CDH5 [cadherin 5], CD93 [cluster of differentiation 93], ICAM2 [intracellular adhesion molecule 2], GP1BB [glycoprotein 1b platelet subunit beta]), while another approached significance (RSPO3 [R-Spondin 3]). A composite score based on 3 of these BEC proteins accounted for 11% of variation in white matter lesion volumes in BLSA participants. We replicated the associations between the BEC composite score, CDH5, and RSPO3 with white matter lesion volumes in ARIC, and further demonstrated that the BEC composite score and RSPO3 were associated with the presence of ≥1 cerebral microhemorrhages. We also showed that the BEC composite score, CDH5, and RSPO3 were associated with 25-year dementia risk. CONCLUSIONS: In addition to identifying BEC proteins in plasma that relate to cerebral small vessel disease and dementia risk, we developed a composite score of plasma BEC proteins that may be used to estimate blood-brain barrier integrity and risk for adverse neurovascular outcomes.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
去有风的地方完成签到 ,获得积分10
3秒前
上下完成签到 ,获得积分10
5秒前
王娟秀完成签到 ,获得积分10
6秒前
YL完成签到,获得积分10
8秒前
NexusExplorer应助小王采纳,获得10
9秒前
9秒前
sl完成签到,获得积分10
9秒前
CC完成签到,获得积分10
10秒前
自信松思完成签到 ,获得积分10
11秒前
荣枫完成签到,获得积分10
11秒前
11秒前
火火火木完成签到 ,获得积分10
12秒前
大模型应助妖孽宇采纳,获得10
12秒前
14秒前
积极行天发布了新的文献求助50
14秒前
受伤凌蝶发布了新的文献求助10
17秒前
fusucheng完成签到,获得积分10
18秒前
koi完成签到,获得积分20
18秒前
18秒前
聪明摩托完成签到,获得积分10
18秒前
阿纯完成签到,获得积分10
19秒前
20秒前
肱二头肌完成签到,获得积分10
21秒前
22秒前
小王发布了新的文献求助10
22秒前
多情自古空余恨完成签到,获得积分10
23秒前
Qionglin完成签到,获得积分10
25秒前
Bao完成签到 ,获得积分10
26秒前
26秒前
初夏微凉发布了新的文献求助30
26秒前
27秒前
书霂完成签到,获得积分10
27秒前
优秀含羞草完成签到,获得积分10
28秒前
宓沂完成签到,获得积分10
28秒前
vivre223完成签到,获得积分10
28秒前
量子星尘发布了新的文献求助10
29秒前
受伤凌蝶完成签到,获得积分10
30秒前
wenjiejiang完成签到,获得积分10
31秒前
31秒前
zly完成签到 ,获得积分10
32秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038388
求助须知:如何正确求助?哪些是违规求助? 3576106
关于积分的说明 11374447
捐赠科研通 3305798
什么是DOI,文献DOI怎么找? 1819322
邀请新用户注册赠送积分活动 892672
科研通“疑难数据库(出版商)”最低求助积分说明 815029