Wang Yan, Li Fangyu, Qin Qi, Li Tingting, Wang Qi, Li Yan, Li Ying, Jia Jianping
Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases.
Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases; Beijing Key Laboratory of Geriatric Cognitive Disorders; Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University; Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University; Key Laboratory of Neurodegenerative Diseases, Ministry of Education.
J Prev Alzheimers Dis. 2025 Apr;12(4):100065. doi: 10.1016/j.tjpad.2025.100065. Epub 2025 Jan 17.
Apolipoprotein E ε4 (APOE ε4) bring the higher risk of Alzheimer' Disease (AD). It is essential to evaluate whether the diagnostic performances and critical values of cerebrospinal fluid (CSF) biomarkers are influenced by APOE ε4, which has guiding significance for the clinical practical application.
The differences in CSF biomarkers and their performances between APOE ε4 carriers and non-carriers in distinguishing AD, mild cognitive impairment (MCI) and preclinical AD from normal controls (NCs) were analyzed. The receiver operating characteristic (ROC) curves were generated to compare the area under the curve (AUC) between APOE ε4 carriers and non-carriers, as well as the critical values corresponding Youden Index.
In a cross sectional convenience sample of 1610 participants, lower Aβ42 and Aβ42/Aβ40 and higher p-Tau 181/Aβ42 in CSF were observed among APOE ε4 carriers than non-carriers in NC, MCI, and AD groups (P< 0.05). The performance of CSF p-tau/Aβ42 in distinguishing MCI from NC among APOE ε4 carriers was superior to non-carriers [AUC: 0.714 (95%CI: 0.673- 0.752) vs 0.600 (95%CI: 0.564- 0.634), P< 0.001], although it was similar in distinguishing AD from NC between APOE ε4 carriers and non-carriers [AUC: 0.874 (95%CI: 0.835-0.906) vs 0.876 (95%CI: 0.843- 0.904)]. In the longitudinal cohort of 254 participants, the association of CSF Aβ42, Aβ42/Aβ40 and p-Tau181/Aβ42 with cognitive decline were stronger in APOE ε4 carriers compared to non-carriers (P< 0.05). Meanwhile, the critical values were different depending on APOE genotype.
The CSF level of p-Tau181/Aβ42 was significantly different between APOE ε4 carriers and non-carriers at different stages of AD. The results indicate that the performances of CSF biomarkers are influenced by APOE ε4, which should be considered in the practical application.
载脂蛋白Eε4（APOEε4）会增加患阿尔茨海默病（AD）的风险。评估脑脊液（CSF）生物标志物的诊断性能和临界值是否受APOEε4影响至关重要，这对临床实际应用具有指导意义。
分析了APOEε4携带者和非携带者在区分AD、轻度认知障碍（MCI）和临床前期AD与正常对照（NC）时CSF生物标志物的差异及其性能。绘制受试者工作特征（ROC）曲线，比较APOEε4携带者和非携带者之间的曲线下面积（AUC），以及对应约登指数的临界值。
在1610名参与者的横断面便利样本中，在NC、MCI和AD组中，APOEε4携带者脑脊液中的Aβ42和Aβ42/Aβ40水平低于非携带者，而p-Tau 181/Aβ42水平高于非携带者（P<0.05）。在区分MCI与NC方面，APOEε4携带者中CSF p-tau/Aβ42的性能优于非携带者[AUC：0.714（95%CI：0.673-0.752）对0.600（95%CI：0.564-0.634），P<0.001]，尽管在区分AD与NC方面，APOEε4携带者和非携带者相似[AUC：0.874（95%CI：0.835-0.906）对0.876（95%CI：0.843-0.904）]。在254名参与者的纵向队列中，与非携带者相比，APOEε4携带者中CSF Aβ42、Aβ42/Aβ40和p-Tau181/Aβ42与认知衰退的关联更强（P<0.05）。同时，临界值因APOE基因型而异。
在AD的不同阶段，APOEε4携带者和非携带者之间CSF中p-Tau181/Aβ42水平存在显著差异。结果表明，CSF生物标志物的性能受APOEε4影响，在实际应用中应予以考虑。
