Misfolding of superoxide dismutase-1 (SOD1) has been correlated with many neurodegenerative diseases, such as Amyotrophic lateral sclerosis's and Alzheimer's among others. However, it is unclear whether misfolded SOD1 plays a role in another neurodegenerative disease of white matter lesions (WMLs). In this study, a sensitive and specific method based on SERS technique was proposed for quantitative detection of misfolded SOD1 content in WMLs. To fabricate the double antibodysandwich substrates for SERS detection, gold nanostars modified with capture antibody were immobilized on glass substrates to prepare active SERS substrates, and then SERS probes conjugated with a Raman reporter and a specific target antibody were coupled with active SERS substrates. This SERS substrates had been employed for quantitative detection of misfolded SOD1 levels in WMLs and exhibited excellent stability, reliability, and accuracy. Moreover, experimental results indicated that the level of misfolded SOD1 increased with the increase in age and the degree of WMLs. Hence, misfolded SOD1 may be a potential blood marker for WMLs and aging. Meanwhile, SERS-based gold nanostars have great clinical application potential in the screening, diagnosis and treatment of WMLs.

超氧化物歧化酶 1 (SOD1) 的错误折叠与许多神经退行性疾病相关，例如肌萎缩侧索硬化症和阿尔茨海默氏症等。然而，尚不清楚错误折叠的 SOD1 是否在另一种白质病变 (WML) 的神经退行性疾病中起作用。在本研究中，提出了一种基于 SERS 技术的灵敏特异方法，用于定量检测 WML 中错误折叠的 SOD1 含量。为了制备用于SERS检测的双抗体夹心基板，将捕获抗体修饰的金纳米星固定在玻璃基板上制备活性SERS基板，然后将与拉曼报告基因和特定目标抗体偶联的SERS探针与活性SERS基板偶联。该 SERS 基底已用于定量检测 WML 中错误折叠的 SOD1 水平，并表现出出色的稳定性、可靠性和准确性。此外，实验结果表明，错误折叠的SOD1水平随着年龄和WMLs程度的增加而增加。因此，错误折叠的 SOD1 可能是 WML 和衰老的潜在血液标志物。同时，基于SERS的金纳米星在WMLs的筛查、诊断和治疗方面具有巨大的临床应用潜力。