Department of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Huntington Medical Research Institutes, Pasadena, California, USA.
Alzheimers Dement. 2020 Jun;16(6):821-830. doi: 10.1002/alz.12061. Epub 2020 Apr 16.
Blood-brain barrier (BBB) breakdown and loss of brain capillary pericytes contributes to cognitive impairment. Pericytes express platelet-derived growth factor receptor-β (PDGFRβ) that regulates brain angiogenesis and blood vessel stability. Elevated soluble PDGFRβ (sPDGFRβ) levels in cerebrospinal fluid (CSF) indicate pericyte injury and BBB breakdown, which is an early biomarker of human cognitive dysfunction.
A combination of reagents and conditions were tested, optimized, and validated on the Meso Scale Discovery electrochemiluminescence platform to develop a new sPDGFRβ immunoassay that was used to measure sPDGFRβ in human CSF from 147 individuals.
We developed standard operating procedures for a highly sensitive and reproducible sPDGFRβ immunoassay with a dynamic range from 100 to 26,000 pg/mL, and confirmed elevated CSF sPDGFRβ levels in individuals with cognitive dysfunction.
This assay could be applied at different laboratories to study brain pericytes and microvascular damage in relation to cognition in disorders associated with neurovascular and cognitive dysfunction.
血脑屏障（BBB）的破坏和脑毛细血管周细胞的丧失导致认知障碍。周细胞表达血小板衍生生长因子受体-β（PDGFRβ），它调节脑血管生成和血管稳定性。脑脊液（CSF）中可溶性 PDGFRβ（sPDGFRβ）水平升高表明周细胞损伤和 BBB 破坏，这是人类认知功能障碍的早期生物标志物。
在 Meso Scale Discovery 电化学发光平台上测试、优化和验证了一系列试剂和条件，以开发一种新的 sPDGFRβ免疫分析方法，用于测量 147 个人的人 CSF 中的 sPDGFRβ。
我们开发了一种高灵敏度和重现性的 sPDGFRβ免疫分析的标准操作程序，其动态范围为 100 至 26,000 pg/mL，并证实认知功能障碍个体的 CSF sPDGFRβ 水平升高。
该检测方法可在不同实验室应用，以研究与认知障碍相关的神经血管和认知功能障碍疾病中与脑周细胞和微血管损伤相关的认知功能。
