Hypocretin and brain β-amyloid peptide interactions in cognitive disorders and narcolepsy
Hypocretin and brain β-amyloid peptide interactions in cognitive disorders and narcolepsy
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DOI：
10.3389/fnagi.2014.00119
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发表时间：
2014-06-11
影响因子：
4.8
通讯作者：
Gabelle, Audrey
中科院分区：
文献类型：
--
作者：
Dauvilliers, Yves A.;Lehmann, Sylvain;Gabelle, Audrey
目的：研究认知异常和下丘脑泌素缺乏性发作性睡病（NC）患者脑脊液（CSF）阿尔茨海默病（AD）生物标志物和下丘脑泌素-1水平之间的关系，评估诊断准确性，并确定与睡眠障碍的相关性。背景：AD患者经常出现睡眠障碍。在AD小鼠模型中，脑β-淀粉样蛋白（AO聚集体）和觉醒相关神经递质下丘脑泌素之间的相互作用已被报道。方法：91例认知患者（37例AD，16例轻度认知障碍MCI转化为AD，38例其他痴呆）和15例老年NC患者被招募。患者被诊断为对CSF结果不知情。测量CSF A（β 42）、总tau、ptau（181）和下丘脑泌素-1。结果：AD和MCI患者的CSF 442水平较低，但tau和P-tau水平较高。与其他痴呆相比，AD所致MCI患者的CSF下丘脑泌素-1水平较高，晚期AD患者的趋势相似。CSF下丘脑泌素-1与AD所致的AD/MCI显著且独立相关，完全校正后OR为2.70，超过A（β 42）。在晚期AD中，A（β 42）与下丘脑泌素-1水平呈正相关。未发现睡眠障碍与CSF生物标志物之间存在关联。没有NC患者达到病理截止值为442，分别有一个和四个NC以上的tau和P-tau截止值和hypocretin-1和其他biomarkers.Conclusions之间没有相关性：我们的研究结果表明，442和hypocretin-1在AD过程中的病理生理关系，在疾病的早期阶段具有较高的CSF hypocretin-1水平。需要进一步的纵向研究来验证这些生物标志物的相互作用，并确定因果关系和觉醒/睡眠行为在淀粉样斑块调节中的作用。
Objective: To examine relationships between cerebrospinal fluid (CSF) Alzheimer' disease (AD) biomarkers and hypocretin-1 levels in patients with cognitive abnormalities and hypocretin-deficient narcolepsy-cataplexy (NC), estimate diagnostic accuracy, and determine correlations with sleep disturbances.Background: Sleep disturbances are frequent in AD. Interactions between brain beta-amyloid (AO aggregation and a wake-related neurotransmitter hypocretin have been reported in a mouse model of AD.Methods: Ninety-one cognitive patients (37 AD, 16 mild cognitive impairment MCI that converts to AD, 38 other dementias) and 15 elderly patients with NC were recruited. Patients were diagnosed blind to CSF results. CSF A(beta 42), total tau, ptau(181), and hypocretin-1 were measured. Sleep disturbances were assessed with questionnaires in 32 cognitive patients.Results: Lower CSF 442 but higher tau and P-tau levels were found in AD and MCI compared to other dementias. CSF hypocretin-1 levels were higher in patients with MCI due to AD compared to other dementias, with a similar tendency for patients with advanced AD. CSF hypocretin-1 was significantly and independently associated with AD/MCI due to AD, with an OR of 2.70 after full adjustment, exceeding that for A(beta 42). A(beta 42) correlated positively with hypocretin-1 levels in advanced stage AD. No association was found between sleep disturbances and CSF biomarkers. No patients with NC achieved pathological cutoffs for 442, with respectively one and four patients with NC above tau and P-tau cutoffs and no correlations between hypocretin-1 and other biomarkers.Conclusions: Our results suggest a pathophysiological relationship between 442 and hypocretin-1 in the AD process, with higher CSF hypocretin-1 levels in early disease stages. Further longitudinal studies are needed to validate these biomarker interactions and to determine the cause-effect relationship and the role of wake/sleep behavior in amyloid plaque regulation.