Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Curr Alzheimer Res. 2018;15(10):938-950. doi: 10.2174/1567205015666180601090533.
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.
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.
The APOE genotype and morning plasma melatonin, cortisol, homocysteine, and prolactin concentrations were measured in 85 patients with AD and 44 elderly controls.
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.
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.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其发病机制复杂，常伴有抑郁等共病。目前认为，载脂蛋白 E（APOE）基因编码的 ε4 等位基因的存在是散发性 AD 发展的最强遗传风险因素。褪黑素、皮质醇、同型半胱氨酸和催乳素被认为是与应激和年龄相关疾病相关的风险因素或生物标志物。
研究 AD 患者伴或不伴抑郁时 APOE 基因型与血浆生物标志物之间的相互作用，以帮助理解 AD 病理生理学中各种分子机制的相互依存关系。
在 85 例 AD 患者和 44 例老年对照组中测量了 APOE 基因型和早晨血浆褪黑素、皮质醇、同型半胱氨酸和催乳素浓度。
证实 AD 与 APOE 的等位基因（ε4）或基因型（ε3/ε4 或 ε4/ε4）频率之间存在显著相关性。与对照组相比，AD 患者的血浆同型半胱氨酸和皮质醇水平显著升高，与是否存在共病抑郁症状或痴呆严重程度无关。AD 患者的血浆褪黑素浓度明显低于对照组，但对照组不携带 APOE ε4 等位基因，无论是否存在抑郁或 AD 痴呆的严重程度。
我们的研究结果表明，存在一种鲜为人知的特定 APOE 介导的机制，该机制可增加携带 APOE ε4 等位基因的 AD 患者亚组的血浆褪黑素水平。
