Alzheimer's disease with sleep insufficiency:a cross-sectional study on correlations among clinical characteristics,orexin,its receptors,and the bloodbrain barrier  

作　　者：Peng Guo Wen-Jing Zhang Teng-Hong Lian Wei-Jiao Zhang Ming-Yue He Ya-Nan Zhang Yue Huang Du-Yu Ding Hui-Ying Guan Jing-Hui Li Dan-Ning Li Dong-Mei Luo Wei-Jia Zhang Hao Yue Xiao-Min Wang Wei Zhang 

机构地区：[1]Center for Cognitive Neurology,Department of Neurology,Beijing Tiantan Hospital,Capital Medical University,Beijing,China [2]Department of Neurology,Beijing Tiantan Hospital,Capital Medical University,Beijing,China [3]Department of Blood Transfusion,Beijing Tiantan Hospital,Capital Medical University,Beijing,China [4]Department of Pharmacology,School of Medical Sciences,Faculty of Medicine&Health,University of New South Wales,Sydney,Australia [5]China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University,Beijing,China [6]Department of Physiology,Capital Medical University,Beijing,China [7]Center of Parkinson’s Disease,Beijing Institute for Brain Disorders,Beijing,China [8]Beijing Key Laboratory on Parkinson’s Disease,Beijing,China

出　　处：《Neural Regeneration Research》2023年第8期1757-1762,共6页中国神经再生研究（英文版）

基　　金：supported by the National Key Research and Development Program of China,Nos.2016YFC1306300(to XMW),2016YFC1306000;the National Key R&D Program of China-European Commission Horizon 2020,No.2017YFE0118800-779238(to YXW);the Notional Natural Science Foundation of Chino,Nos.81970992(to WZ),81571229(to WZ),81071015(to WZ),30770745(to WZ);Capital's Funds for Health Improvement and Research(CFH),No.2022-2-2048(to WZ);the Key Technology R&D Program of Beijing Municipal Education Commission,No.kz201610025030(to WZ);the Natural Science Foundation of Beijing,No.7082032(to WZ);the Key Project of the Natural Science Foundation of Beijing,No.4161004(to WZ);Capitol Clinical Characteristic Applicotion Research,No.Z121107001012161(to WZ);Project of Scientific and Technological Development of Traditional Chinese Medicine in Beijing,No.JJ2018-48(to WZ);High Level Technical Personnel Training Project of Beijing Health System of China,No.2009-3-26(to WZ);Excellent Personnel Training Project of Beijing,No.20071D0300400076(to WZ);Important National Science&Technology Specific Project,No.2011ZX09102-003-01(to WZ);Beijing Healthcare Research Project,No.JING-15-2(to WZ);Basic-Clinicol Research Cooperation Funding of Capitol Medical University of China,Nos.2015-JL-PT-X04(to WZ),10JL49(to WZ),14JL15(to WZ);the Natural Science Foundation of Capital Medical University;Beijing;China,No.PYZ2018077(to PG);Youth Research Fund of Beijing Tianton Hospital of Capital Medical University of China,Nos.2015-YQN-14(to PG),2015-YQN-15,2015-YQN-17。

摘　　要：Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.

关 键 词：Alzheimer's disease blood-brain barrier cerebrospinal fluid clinical characteristics cognitive function matrix metalloproteinases matrix metalloproteinase-3 neuropsychiatric symptoms orexin signaling sleep insufficiency 

分 类 号：R749.16[医药卫生—神经病学与精神病学]