Lei Dan, Mao Chenhui, Li Jie, Huang Xinying, Sha Longze, Liu Caiyan, Dong Liling, Xu Qi, Gao Jing
State Key Laboratory of Complex Severe and Rare Diseases, Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Neurol. 2023 Jan 9;13:1030019. doi: 10.3389/fneur.2022.1030019. eCollection 2022.
Alzheimer's disease (AD) is one of the highly concerned degenerative disorders in recent decades. Though vast amount of researches has been done in various aspects, early-onset subtype, however, needs more investigation in diagnosis for its atypical manifestations and progression process. Fundamental CSF biomarkers of early-onset AD are explored in PUMCH dementia cohort to depict its laboratory characteristics.
A total of 125 individuals (age of onset <65 years old) from PUMCH dementia cohort were recruited consecutively and classified into AD, non-AD dementia, and control groups. Levels of amyloid-β 42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau) were measured using ELISA INNOTEST (Fujirebio, Ghent, Belgium). Students' -test or non-parametric test are used to evaluate the differences between groups. Area under curve (AUC) of receiver operating characteristic (ROC) curve was introduced to prove the diagnostic powers of corresponding markers. Logistic regression is used to establish diagnostic model to combine several markers together to promote the diagnostic power.
The average of all three biomarkers and two calculated ratios (t-tau/Aβ42, p-tau/Aβ42) were statistically different in the AD group compared with the other two groups ( < 0.01). From our data, we were able to provide cutoff values (Aβ42 < 570.9 pg/mL; p-tau > 56.49 pg/mL; t-tau > 241.6 pg/mL; t-tau/Aβ42 > 0.529; p-tau/Aβ42 > 0.0846) with acceptable diagnostic accuracy compared to other studies. Using a combination of biomarkers and logistic regression (area under curve 0.951), we were able to further improve diagnostic efficacy.
Our study supports the diagnostic usefulness of biomarkers and defined cutoff values to diagnose early-onset AD. We showed that the ratios of t-tau/Aβ42 and p-tau/Aβ42 are more sensitive than relying on Aβ42 levels alone, and that we can further improve diagnostic accuracy by combining biomarkers.
阿尔茨海默病（AD）是近几十年来备受关注的退行性疾病之一。尽管在各个方面已经进行了大量研究，但早发型亚型由于其非典型表现和进展过程，在诊断方面仍需要更多研究。在北京协和医院痴呆队列中探索早发型AD的基础脑脊液生物标志物，以描述其实验室特征。
连续招募北京协和医院痴呆队列中的125名个体（发病年龄<65岁），并将其分为AD组、非AD痴呆组和对照组。使用ELISA INNOTEST（富士瑞必欧，比利时根特）检测淀粉样β蛋白42（Aβ42）、总tau蛋白（t-tau）和磷酸化tau蛋白（p-tau）的水平。采用学生t检验或非参数检验评估组间差异。引入受试者操作特征（ROC）曲线下面积（AUC）来证明相应标志物的诊断能力。使用逻辑回归建立诊断模型，将多个标志物组合在一起以提高诊断能力。
与其他两组相比，AD组中所有三种生物标志物以及两个计算比值（t-tau/Aβ42、p-tau/Aβ42）的平均值在统计学上存在差异（<0.01）。根据我们的数据，与其他研究相比，我们能够提供具有可接受诊断准确性的临界值（Aβ42<570.9 pg/mL；p-tau>56.49 pg/mL；t-tau>241.6 pg/mL；t-tau/Aβ42>0.529；p-tau/Aβ42>0.0846）。使用生物标志物和逻辑回归的组合（曲线下面积为0.951），我们能够进一步提高诊断效能。
我们的研究支持生物标志物和定义的临界值对早发型AD的诊断有用性。我们表明，t-tau/Aβ42和p-tau/Aβ42的比值比仅依赖Aβ42水平更敏感，并且我们可以通过组合生物标志物进一步提高诊断准确性。
