SAGE-Hindawi Access to Research Journal of Aging Research Volume 2011, Article ID 383091, 4 pages doi:10.4061/2011/383091 Review Article CLOCK Genes and Circadian Rhythmicity in Alzheimer Disease J. Thome,1 A. N. Coogan,2 A. G. Woods,3 C. C. Darie,3 and F. Ha¨ßler4 1 Department of Psychiatry, University of Rostock, Gehlsheimerstraße 20, 18147 Rostock, Germany 2 Department of Psychology, National University of Ireland, Maynooth, Maynooth, Ireland 3 Biochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY 13699, USA 4 Department of Child and Adolescent Psychiatry and Neurology, University of Rostock, 18147 Rostock, Germany Correspondence should be addressed to J. Thome, johannes.thome@med.uni-rostock.de Received 2 August 2011; Accepted 16 August 2011 Academic Editor: Aurel Popa-Wagner Copyright © 2011 J. Thome et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Disturbed circadian rhythms with sleep problems and disrupted diurnal activity are often seen in patients suﬀering from Alzheimer disease (AD). Both endogenous CLOCK genes and external Zeitgeber are responsible for the maintenance of circadian rhythmicity in humans. Therefore, modiﬁcations of the internal CLOCK system and its interactions with exogenous factors might constitute the neurobiological basis for clinically observed disruptions in rhythmicity, which often have grave consequences for the quality of life of patients and their caregivers. Presently, more and more data are emerging demonstrating how alterations of the CLOCK gene system might contribute to the pathophysiology of AD and other forms of dementia. At the same time, the impact of neuropsychiatric medication on CLOCK gene expression is under investigation. 1. Introduction Alzheimer disease (AD) is the most frequent form of demen- tia and one of the most devastating psychiatric disorders, with an estimated 33.9 million people worldwide aﬀected [1]. With increasing life expectancy, AD prevalence will further rise dramatically within the next decades. While the typical neuropathological features have been well known since their ﬁrst description in 1906 [2], the complex pathophysiology of this condition is still not fully understood. Some progress has been made in elucidating possible risk genes [3, 4] as well as the role of advanced glycation end products [5, 6], amyloid plaques [7], neuroﬁbrillary tangles [8], and other pathological factors which probably interact within the so- called “pathogenic cascade” [9]. Further, presently available treatment strategies are not suﬃcient and not satisfying as they, at best, slow down the progression of the symptoms but do not provide an option to reverse them. Intervention may frequently occur at advanced stages of neurodegeneration which are no longer possible to alleviate [10]. Additionally, treatments are often associated with a plethora of side eﬀects. From a clinical point of view, patients, their families, carers, and health professionals are confronted with severe challenges in managing the condition. One such typical challenge is the disturbed diurnal-nocturnal rhythm of many Alzheimer patients [11–13]. Interestingly, circadian CLOCK gene polymorphisms might be linked to sleep-wake disturbances in Alzheimer patients, although the authors of a recent paper focusing on this hypothesis reported largely negative ﬁndings for the 122 circadian-related poly- morphisms included [14]. The molecular and cellular basis of circadian rhythmicity consists of a complex interaction between various transcription factors, commonly described as CLOCK genes, which represent an internal timekeeping system that interacts with external synchronising factors: the so-called Zeitgebers [15, 16]. Via this interaction, humans and many animals maintain a recurring 24-hour (circadian) system for a plethora of biological and behavioural processes. Desynchronisation can be caused by various factors such as shiftwork, airtravelling through time zones, substances and medication, and neuropsychiatric disorders [17, 18]. Severe desynchronisation is regularly observed in patients suﬀering from AD and, therefore, the elucidation of the role of CLOCK genes in this condition might contribute to a signiﬁcantly improved understanding of its underlying pathomechanisms.