摘要
背景:阿尔茨海默病(AD)是一种累进性神经退行性疾病,发病机制复杂,是抑郁症等常见疾病,人们普遍认为,载脂蛋白e(apolipoprotein e,APOE)基因ε4等位基因的存在是散发性AD发生的最强烈的遗传危险因素,褪黑素、皮质醇、同型半胱氨酸和催乳素可能是应激和年龄相关疾病的危险因素或生物标志物。 目的:研究ADD患者APOE基因型与血浆标志物之间的相互关系,为进一步了解AD发病机制之间的相互依存关系产生的作用。 方法:测定85例AD患者和44例老年对照组APOE基因型和晨间褪黑素、皮质醇、同型半胱氨酸和催乳素浓度。 结果:AD与APOE的等位基因(ε4)或基因型(ε3/ε4或ε4/ε4)频率有显著相关性,AD患者血浆同型半胱氨酸和皮质醇水平显著高于对照组,与伴发抑郁症状或痴呆严重程度无关,AD患者血浆褪黑素浓度明显低于对照组(非携带者)。APOEε4等位基因,与AD中抑郁或痴呆的严重程度无关。 结论:我们的发现表明,在携带APOEε4等位基因的AD患者中,存在一种鲜为人知的APOE介导的升高血浆褪黑素水平的机制。
关键词: 阿尔茨海默病,载脂蛋白e,皮质醇,同型半胱氨酸,褪黑素,催乳素。
Current Alzheimer Research
Title:Interplay between the APOE Genotype and Possible Plasma Biomarkers in Alzheimer’s Disease
Volume: 15 Issue: 10
关键词: 阿尔茨海默病,载脂蛋白e,皮质醇,同型半胱氨酸,褪黑素,催乳素。
摘要: Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis and a common occurrence of comorbid diseases such as depression. It is accepted that the presence of the ε4 allele of the gene that encodes apolipoprotein E (APOE) is the strongest genetic risk factor for the development of sporadic AD. Melatonin, cortisol, homocysteine, and prolactin are presumed to be risk factors or biomarkers for stress- and age-related disorders.
Objective: The interplay between the APOE genotype and plasma biomarkers was examined in patients with AD presenting with or without depression to contribute to understanding the interdependence of various molecular mechanisms in the pathophysiology of AD.
Method: The APOE genotype and morning plasma melatonin, cortisol, homocysteine, and prolactin concentrations were measured in 85 patients with AD and 44 elderly controls.
Results: A significant association between AD and the allele (ε4) or genotype (ε3/ε4 or ε4/ε4) frequencies of APOE was confirmed. Plasma homocysteine and cortisol levels were significantly increased in patients with AD compared to those in controls, independent of the presence of comorbid depressive symptoms or the severity of dementia. Significantly lower plasma melatonin concentration was found in patients with AD but not in controls, who were noncarriers of the APOE ε4 allele, regardless of the presence of depression or the severity of dementia in AD.
Conclusion: Our findings indicate the existence of a little-known specific APOE-mediated mechanism that increases the plasma melatonin level in a subgroup of patients with AD who are carriers of the APOE ε4 allele.
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Interplay between the APOE Genotype and Possible Plasma Biomarkers in Alzheimer’s Disease, Current Alzheimer Research 2018; 15 (10) . https://dx.doi.org/10.2174/1567205015666180601090533
DOI https://dx.doi.org/10.2174/1567205015666180601090533 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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