Wang Mengxue, Zhang Zhengsheng, Shi Yachen, Shu Hao, Xie Chunming, Ren Qingguo, Wang Zan
Department of Neurology, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine, Southeast University, Nanjing, 210009, People's Republic of China.
Department of Neurology, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi, People's Republic of China.
Neuropsychiatr Dis Treat. 2025 May 5;21:999-1010. doi: 10.2147/NDT.S516476. eCollection 2025.
Patients with amnestic mild cognitive impairment (aMCI) are thought to be highly susceptible to developing Alzheimer's disease (AD). The study aimed to investigate the possibilities of plasma-biomarkers for individual patient identification of aMCI and prediction of episodic memory.
We recruited 87 healthy controls and 68 aMCI patients in this study; and 22/68 aMCI patients completed 3-year follow-up visits, with six aMCI patients converting to AD. An ultrasensitive quantitative method was employed to measure the levels of plasma biomarkers.
Relative to healthy controls, the aMCI patients showed significantly higher levels of plasma neurofilament light (NfL) and lower levels of plasma 40, 42 and 42/40 ratio (all values <0.01). Using multivariate relevance vector regression models, we further demonstrated plasma biomarkers could accurately predict baseline Rey's Auditory Verbal Learning Test-20 min delayed recall (AVLT-DR) scores (r = 0.362, value <0.001) and 3-year longitudinal AVLT-DR changes (r = 0.365, value <0.001) for individual aMCI patients; plasma-indicators contributed most to the predictions including total-tau and NfL. Finally, by using support vector machine model, the combination of plasma 42/40, mini-mental state examination (MMSE) score, and hippocampal/parahippocampal volume had the highest accuracy of 77.42% (sensitivity = 72.06%, specificity = 81.61%) for identifying aMCI patients.
We provided support to the use of plasma total-tau and NfL as simple biomarkers to predict the severity of episodic memory deficit for individual aMCI patients and aMCI progression, and further demonstrated that the combination of plasma 42/40, hippocampal/parahippocampal volume, and MMSE score could serve as an integrated screening tool to select aMCI individuals.
遗忘型轻度认知障碍（aMCI）患者被认为极易发展为阿尔茨海默病（AD）。本研究旨在探讨血浆生物标志物用于个体aMCI患者识别及情景记忆预测的可能性。
本研究招募了87名健康对照者和68名aMCI患者；68名aMCI患者中的22名完成了3年的随访，其中6名aMCI患者转变为AD。采用超灵敏定量方法测量血浆生物标志物水平。
相对于健康对照者，aMCI患者血浆神经丝轻链（NfL）水平显著更高，血浆40、42及42/40比值水平更低（所有P值<0.01）。使用多变量相关向量回归模型，我们进一步证明血浆生物标志物能够准确预测个体aMCI患者的基线雷伊听觉词语学习测验-20分钟延迟回忆（AVLT-DR）分数（r = 0.362，P值<0.001）以及3年纵向AVLT-DR变化（r = 0.365，P值<0.001）；血浆指标对预测贡献最大，包括总tau蛋白和NfL。最后，通过使用支持向量机模型，血浆42/40、简易精神状态检查表（MMSE）分数以及海马体/海马旁回体积的组合在识别aMCI患者方面具有最高准确率，为77.42%（敏感性 = 72.06%，特异性 = 81.61%）。
我们支持将血浆总tau蛋白和NfL作为简单生物标志物用于预测个体aMCI患者情景记忆缺陷的严重程度及aMCI进展，并且进一步证明血浆42/40、海马体/海马旁回体积和MMSE分数的组合可作为筛选aMCI个体的综合工具。
