## 1 Introduction  
Sporadic Alzheimer's disease (AD) is the most common form of dementia, with its causes remaining to be established. Interactions among multiple genetic, epigenetic, and environmental factors seem to play a role, especially in late-onset forms. Since progression of AD is related to age, great attention is now focussed on the research of various age-related contributors, which could be controlled and perhaps managed. Among these, healthy aging and lifestyle, as well as optimal sleep, are of major relevance. Chronic sleep deprivation (SD) appears to be one of the potential environmental risk factors for AD, with sleep disruptions and fragmentations reported from an early stage. Clinical data indicate that about 45% of AD patients have sleep impairments [1]. Alterations in the sleep-wake cycle were also found in transgenic animal models of AD [2; 3]. Disruption of sleep is known to interfere with learning and memory, among others, through oxidative stress [4], with the latter known to play a key role in the age-related neurodegenerative process as well, with amyloid \(\beta\) peptide (A\(\beta\)) acting as a key inducer of oxidative damage [5; 6]. Recently, correlation between the physiological levels of A\(\beta\) and the sleep-wake cycle have been also suggested [1], with acute SD significantly increasing total A\(\beta\) levels, while chronic SD promotes A\(\beta\) aggregation in animals [7]. Chronic SD may also enhance A\(\beta\) deposition in human brain [8]. Sleep hormones such as orexin and melatonin (both involved in sleep regulation) applied in vivo in various transgenic animal models of AD or in vitro on hippocampal neurons can influence levels of soluble A\(\beta\), or alleviate its disruptive effects. In the context of plaque formation, their therapeutic use has been considered as an effective inhibitor of nucleation of plaques, but ineffective after plaque formation [7; 9; 10; 11; 12; 13; 14]. Finally, the link between SD and protein tau has been shown recently, with chronic SD of adult or old transgenic animals increasing the level of phosphorylated tau [15; 16]. Supplementation of melatonin in vivo has been also reported to improve working memory and arrest hyperphosphorylation of tau [17; 18]. The N-methyl-D-aspartate (NMDA) receptor-nitric oxide (NO) pathway is involved in both the sleep-wake cycle and AD pathobiology. Glutamate is the most common excitatory neurotransmitter in the brain, activating NMDA (and several other) receptors [19]. Surprisingly, little is known about glutamatergic regulation of sleep and wakefulness. It has been reported that levels of glutamate in some areas of the rat cortex increase during wakefulness and rapid eye movement (REM) sleep, and decrease during non-REM sleep [20], with SD over 6-12 h increasing glutamate levels in the hippocampus and thalamus [21]. During 3 h SD period, glutamate levels in the prefrontal cortex initially exhibit the progressive rise, however, as SD increases, the levels cease to increase and start to decrease [22]. It is suggested that SD can influence NMDA receptors, especially via alterations in surface expression or subunits composition, particularly of NR1, NR2A, and NR2B subunits [23]. In the rat hippocampus, 4 h SD increases NR2A/NR2B ratio as well as total NR2A, whereas 5 h SD does not induce changes. Prolonged (72 h) SD, on the other hand, reduces surface expression of NR1 and NR2A subunits of NMDA receptors. NR2B expression is also decreased in the hippocampus because of SD [23; 24; 25]. In the rat cortex, 8 h SD leads to upregulation of NR2A subunit transcripts [26]. Similar to sleep, subunits composition of NMDA receptors is altered during normal aging and AD. In the cortex or hippocampus of old compared to young rodents, NR1 levels are reduced, while NR2A or NR2B levels do not seem to alter consistently [27; 28; 29]. Indeed, NR2B levels were reduced, e.g., in the cortex, but increased in the hippocampus [27].