%0 Journal Article
%T CLOCK Genes and Circadian Rhythmicity in Alzheimer Disease
%A J. Thome
%A A. N. Coogan
%A A. G. Woods
%A C. C. Darie
%A F. H£¿£¿ler
%J Journal of Aging Research
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/383091
%X 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 dementia 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¨C13]. 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 polymorphisms included [14]. The molecular and cellular basis of circadian rhythmicity
%U http://www.hindawi.com/journals/jar/2011/383091/