Athanasaki Athanasia, Tsantzali Ioanna, Kroupis Christos, Theodorou Aikaterini, Boufidou Fotini, Constantinides Vasilios C, Tzartos John S, Tzartos Socrates J, Velonakis Georgios, Zompola Christina, Michalopoulou Amalia, Paraskevas Panagiotis G, Bonakis Anastasios, Giannopoulos Sotirios, Moutsatsou Paraskevi, Tsivgoulis Georgios, Kapaki Elisabeth, Paraskevas George P
2nd Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" General University Hospital, 12462 Athens, Greece.
Department of Clinical Biochemistry, School of Medicine, National and Kapodistrian University of Athens, "Attikon" General University Hospital, 12462 Athens, Greece.
Int J Mol Sci. 2025 Aug 1;26(15):7410. doi: 10.3390/ijms26157410.
Alzheimer's disease (AD) is the most common cause of cognitive decline. Among the various susceptibility genes, the gene of apolipoprotein E () is probably the most important. It may be present in three allelic forms, termed ε2, ε3 and ε4, and the most common genotype is the ε3/ε3. Recently, it has been observed that subjects with the ε4/ε4 genotype may show near-full penetrance of AD biology (pathology and biomarkers), leading to the suggestion that ε4 homozygosity may represent a distinct genetic type of AD. The aim of the present study was to investigate the role of ε4 homozygosity or heterozygosity in the presence or absence of the AD biomarker profile in patients with cognitive disorders in the Greek population. A total of 274 patients were included in the study. They underwent genotyping and cerebrospinal fluid (CSF) biomarker profiling. The presence of ε4 was associated with a lower age of symptom onset and decreased amyloid biomarkers (irrespective to AD or non-AD profiles), and predicted the presence of an AD profile by a positive predictive value approaching 100%. In conclusion, the ε4 allele has a significant effect on the risk and clinical parameters of cognitive impairment and AD in the Greek population, while the ε4/ε4 genotype may be highly indicative of the (co)existence of AD in cognitively impaired patients.
阿尔茨海默病（AD）是认知功能衰退最常见的病因。在各种易感基因中，载脂蛋白E（）基因可能最为重要。它可能以三种等位基因形式存在，分别称为ε2、ε3和ε4，最常见的基因型是ε3/ε3。最近，有人观察到，ε4/ε4基因型的个体可能表现出近乎完全的AD生物学特征（病理学和生物标志物），这表明ε4纯合子可能代表一种独特的AD遗传类型。本研究的目的是调查在希腊人群中，ε4纯合子或杂合子在认知障碍患者中是否存在AD生物标志物特征方面所起的作用。共有274名患者纳入本研究。他们接受了基因分型和脑脊液（CSF）生物标志物分析。ε4的存在与症状出现的年龄较低以及淀粉样蛋白生物标志物减少有关（无论是否为AD特征），并且通过接近100%的阳性预测值预测了AD特征的存在。总之，ε4等位基因对希腊人群认知障碍和AD的风险及临床参数有显著影响，而ε4/ε4基因型可能高度提示认知障碍患者中AD的（共）存在。
