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Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease

Circadian Rhythm and Alzheimer’s Disease

Department of Pharmacology, University of Zagreb School of Medicine, Šalata 3, Zagreb 10 000, Croatia
University Hospital for Infectious Diseases, Mirogojska cesta 8, Zagreb 10 000, Croatia
University of Zagreb School of Medicine, Šalata 3, Zagreb 10 000, Croatia
Department of Pathophysiology, University of Zagreb School of Medicine, Kišpaticeva 12, Zagreb 10 000, Croatia
Author to whom correspondence should be addressed.
Med. Sci. 2018, 6(3), 52;
Received: 10 May 2018 / Revised: 19 June 2018 / Accepted: 19 June 2018 / Published: 21 June 2018
(This article belongs to the Collection Advances in the Pathogenesis of Neurodegenerative Diseases)
Alzheimer’s disease (AD) is a neurodegenerative disorder with a growing epidemiological importance characterized by significant disease burden. Sleep-related pathological symptomatology often accompanies AD. The etiology and pathogenesis of disrupted circadian rhythm and AD share common factors, which also opens the perspective of viewing them as a mutually dependent process. This article focuses on the bi-directional relationship between these processes, discussing the pathophysiological links and clinical aspects. Common mechanisms linking both processes include neuroinflammation, neurodegeneration, and circadian rhythm desynchronization. Timely recognition of sleep-specific symptoms as components of AD could lead to an earlier and correct diagnosis with an opportunity of offering treatments at an earlier stage. Likewise, proper sleep hygiene and related treatments ought to be one of the priorities in the management of the patient population affected by AD. This narrative review brings a comprehensive approach to clearly demonstrate the underlying complexities linking AD and circadian rhythm disruption. Most clinical data are based on interventions including melatonin, but larger-scale research is still scarce. Following a pathophysiological reasoning backed by evidence gained from AD models, novel anti-inflammatory treatments and those targeting metabolic alterations in AD might prove useful for normalizing a disrupted circadian rhythm. By restoring it, benefits would be conferred for immunological, metabolic, and behavioral function in an affected individual. On the other hand, a balanced circadian rhythm should provide greater resilience to AD pathogenesis. View Full-Text
Keywords: Alzheimer’s disease; circadian rhythm; melatonin; pathophysiology; sleep Alzheimer’s disease; circadian rhythm; melatonin; pathophysiology; sleep
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MDPI and ACS Style

Homolak, J.; Mudrovčić, M.; Vukić, B.; Toljan, K. Circadian Rhythm and Alzheimer’s Disease. Med. Sci. 2018, 6, 52.

AMA Style

Homolak J, Mudrovčić M, Vukić B, Toljan K. Circadian Rhythm and Alzheimer’s Disease. Medical Sciences. 2018; 6(3):52.

Chicago/Turabian Style

Homolak, Jan, Monika Mudrovčić, Barbara Vukić, and Karlo Toljan. 2018. "Circadian Rhythm and Alzheimer’s Disease" Medical Sciences 6, no. 3: 52.

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