Shang Li, Dong Liling, Huang Xinying, Wang Tianyi, Mao Chenhui, Li Jie, Wang Jie, Liu Caiyan, Gao Jing
Neurological Department, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Front Aging Neurosci. 2023 Mar 31;15:1119070. doi: 10.3389/fnagi.2023.1119070. eCollection 2023.
Apolipoprotein-E () ε4 is a major genetic risk factor for Alzheimer's disease (AD). Current studies, which were mainly based on the clinical diagnosis rather than biomarkers, come to inconsistent conclusions regarding the associations of homozygotes () and cerebrospinal fluid (CSF) biomarkers of AD. In addition, few studies have explored the associations of with plasma biomarkers. Therefore, we aimed to investigate the associations of with fluid biomarkers in dementia and biomarker-diagnosed AD.
A total of 297 patients were enrolled. They were classified into Alzheimer's continuum, AD, and non-AD, according to CSF biomarkers and/or β amyloid PET results. AD was a subgroup of the AD continuum. Plasma Amyloid β (Aβ) 40, Aβ42, glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and phosphorylated tau (P-tau)181 were quantified in 144 of the total population using an ultra-sensitive Simoa technology. We analyzed the associations of on CSF and plasma biomarkers in dementia and biomarker diagnosed AD.
Based on the biomarker diagnostic criteria, 169 participants were diagnosed with Alzheimer's continuum and 128 individuals with non-AD, and among the former, 120 patients with AD. The frequencies were 11.8% (20/169), 14.2% (17/120), and 0.8% (1/128) in Alzheimer's continuum, AD and non-AD, respectively. Only CSF Aβ42 was shown to be decreased in carriers than in non-carriers for patients with AD ( = 0.024). Furthermore, we did not find any associations of with plasma biomarkers of AD and non-AD. Interestingly, we found that in non-AD patients, carriers had lower CSF Aβ42 ( = 0.018) and higher T-tau/Aβ42 ratios ( < 0.001) and P-tau181/Aβ42 ratios ( = 0.002) than non-carriers.
Our data confirmed that of the three groups (AD continuum, AD, and non-AD), those with AD had the highest frequency of genotypes. The was associated with CSF levels of Aβ42 but not tau for AD and non-AD, suggesting that affected the Aβ metabolism of both. No associations between and plasma biomarkers of AD and non-AD were found.
载脂蛋白E（ApoE）ε4是阿尔茨海默病（AD）的主要遗传风险因素。目前的研究主要基于临床诊断而非生物标志物，对于ApoEε4纯合子与AD脑脊液（CSF）生物标志物之间的关联得出了不一致的结论。此外，很少有研究探讨ApoEε4与血浆生物标志物之间的关联。因此，我们旨在研究ApoEε4与痴呆症及生物标志物诊断的AD中的体液生物标志物之间的关联。
共纳入297例患者。根据CSF生物标志物和/或β淀粉样蛋白PET结果，将他们分为阿尔茨海默病连续体、AD和非AD组。AD是阿尔茨海默病连续体的一个亚组。使用超灵敏的Simoa技术对总人群中的144例患者的血浆淀粉样蛋白β（Aβ）40、Aβ42、胶质纤维酸性蛋白（GFAP）、神经丝轻链（NFL）和磷酸化tau（P-tau）181进行了定量分析。我们分析了ApoEε4对痴呆症及生物标志物诊断的AD中CSF和血浆生物标志物的影响。
根据生物标志物诊断标准，169例参与者被诊断为阿尔茨海默病连续体，128例为非AD，其中前者中有120例AD患者。ApoEε4的频率在阿尔茨海默病连续体、AD和非AD组中分别为11.8%（20/169）、14.2%（17/120）和0.8%（1/128）。对于AD患者，仅显示携带ApoEε4者的CSF Aβ42低于非携带者（P = 0.024）。此外，我们未发现ApoEε4与AD和非AD的血浆生物标志物之间存在任何关联。有趣的是，我们发现，在非AD患者中，携带ApoEε4者的CSF Aβ42低于非携带者（P = 0.018），T-tau/Aβ42比值更高（P < 0.001），P-tau181/Aβ42比值更高（P = 0.002）。
我们的数据证实，在三组（阿尔茨海默病连续体、AD和非AD）中，AD患者的ApoEε4基因型频率最高。ApoEε4与AD和非AD的CSF中Aβ42水平相关，但与tau无关，这表明ApoEε4影响两者的Aβ代谢。未发现ApoEε4与AD和非AD的血浆生物标志物之间存在关联。
