Unique Sleep and Circadian Rhythm Dysfunction Neuroinflammatory and Immune Profiles in Alzheimer’s Disease with Mild Cognitive Impairment

Article type: Short Communication

Authors: Pillai, Jagan A.^{a; b; c} | Bena, James^d | Bekris, Lynn M.^e | Foldvary-Schaefer, Nancy^f | Heinzinger, Catherine^f | Rao, Sujata^{g; h} | Rao, Stephen M.^{a; b} | Leverenz, James B.^{a; b; c} | Mehra, Reena^{f; i; j; k; *}

Affiliations: [a] Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, OH, USA | [b] Neurological Institute, Cleveland Clinic, Cleveland, OH, USA | [c] Department of Neurology, Cleveland Clinic, Cleveland, OH, USA | [d] Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA | [e] Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA | [f] Sleep Disorders Center, Neurologic Institute, Cleveland Clinic, Cleveland, OH, USA | [g] Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA | [h] Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA | [i] Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA | [j] Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA | [k] Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

Correspondence: [*] Correspondence to: Reena Mehra, MD, MS, FCCP, FAASM, Professor of Medicine, Director, Sleep Disorders Research, 9500 Euclid Avenue, Cleveland, OH 44195, USA. E-mail: mehrar@ccf.org.

Abstract: Sleep dysfunction has been identified in the pathophysiology of Alzheimer’s disease (AD); however, the role and mechanism of circadian rhythm dysfunction is less well understood. In a well-characterized cohort of patients with AD at the mild cognitive impairment stage (MCI-AD), we identify that circadian rhythm irregularities were accompanied by altered humoral immune responses detected in both the cerebrospinal fluid and plasma as well as alterations of cerebrospinal fluid biomarkers of neurodegeneration. On the other hand, sleep disruption was more so associated with abnormalities in circulating markers of immunity and inflammation and decrements in cognition.

Keywords: Alzheimer’s disease, circadian, immunity, inflammation, neurodegeneration, sleep

DOI: 10.3233/JAD-201573

Journal: Journal of Alzheimer's Disease, vol. 81, no. 2, pp. 487-492, 2021