Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (8): 1757-1762.doi: 10.4103/1673-5374.360250

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

Peng Guo1, #, Wen-Jing Zhang2, #, Teng-Hong Lian1, Wei-Jiao Zhang2, Ming-Yue He2, Ya-Nan Zhang3, Yue Huang2, 4, 5, Du-Yu Ding2, Hui-Ying Guan2, Jing-Hui Li2, Dan-Ning Li2, Dong-Mei Luo2, Wei-Jia Zhang2, Hao Yue2, Xiao-Min Wang6, Wei Zhang1, 5, 7, 8, *#br#   

  1. 1Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 2Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 3Department of Blood Transfusion, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 4Department of Pharmacology, School of Medical Sciences, Faculty of Medicine & Health, University of New South Wales, Sydney, Australia; 5China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 6Department of Physiology, Capital Medical University, Beijing, China; 7Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing, China; 8Beijing Key Laboratory on Parkinson’s Disease, Beijing, China
  • Online:2023-08-15 Published:2023-02-23
  • Contact: Wei Zhang, MD, ttyyzw@163.com.
  • Supported by:
    This work was 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 National Natural Science Foundation of China, 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); Capital Clinical Characteristic Application 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-Clinical Research Cooperation Funding of Capital 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 Tiantan Hospital of Capital Medical University of China, Nos. 2015-YQN-14 (to PG), 2015-YQN-15, 2015-YQN-17.

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Abstract: 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.

Key words: Alzheimer’s disease, blood-brain barrier, cerebrospinal fluid, clinical characteristics, cognitive function, matrix metalloproteinases, matrix metalloproteinase-3, neuropsychiatric symptoms, orexin signaling, sleep insufficiency