In Taiwan, there are about 4-10% people aged 65 years or older suffering from dementia. Alzheimer disease (AD) is the most common cause of dementia. Amyloid-beta (Aβ) is the main component of senile plaques, which are pathological markers of AD, and Aβhas been considered to play the most important role in the pathogenesis of AD. In addition to cognitive dysfunction, AD patients may present behavioral and psychological symptoms of dementia (BPSD). Sleep-wake cycle disturbance, the major outward presentation of circadian rhythm disarrangement, is a very common BPSD in AD patients. In transgenic AD animals, the sun-downing phenomenon, similar to the common manifestation of circadian rhythm disarrangement in AD patients, is also noted. Sleep is important to maintaining neurocognitive functions, including memory consolidation. Different types of learning might be associated with unique sleep-related memory consolidation mechanisms that work in different brain regions and at different sleep stages, such as rapid eye movement (REM) sleep or non-REM, throughout the night. It is well documented that REM sleep, initiated by acetylcholine at brainstem is impaired in AD patients. The accumulation of Aβin AD brain, especially in the brainstem, could impair the REM sleep initiation and maintenance. On the other hand, nitric oxide (NO) produced by NO synthases (NOS) is also important for both REM maintenance and memory consolidation. In our previous study, inducible NOS (iNOS) expression increased in REM sleep among cognitive impairment patients. Therefore, REM sleep and NO pathway should be important for memory consolidation in AD. Sleep disturbance with consequence of memory consolidation impairment could be a crucial cause for further cognitive deterioration for AD patients. In this study, we will explore the behavioral and molecular changes in AD animal to clarify the role of REM sleep in memory consolidation among AD animals and the possible molecular mechanisms for these disarrangements. In summary, the proposal will study AD animals and controls. All of them will undergo polysomnography (PSG)-like examination under regular light-dark cycle and will then undergo memory tests for evaluation of memory consolidation with or without REM deprivation. In the mean time, we will explore the role of Aβaccumulation in REM sleep and memory consolidation by pathological correlation, survey about changes of profiled gene expression and products, including iNOS, eNOS, NO, BDNF, PER1, melatonin, Aβ, tau.
|Effective start/end date||8/1/12 → 7/31/13|
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