Articles Collection about Alzheimer's Disease and Sleep Disorder from Editor-in-Chief Prof. Weidong Le
Our staff editors continue to share brilliant, thoughtful, and meaningful topics and articles in the recommended series.
This week, we would like to share the latest articles about Alzheimer's disease and sleep disorder.
Title: Chronic sleep deprivation altered the expression of circadian clock genes and aggravated Alzheimer's disease neuropathology
Authors: Long Niu, Feng Zhang, Xiaojiao Xu, Yuting Yang, Song Li, Hui Liu, Weidong Le
Type: Original Article
Circadian disruption is prevalent in Alzheimer's disease (AD) and may contribute to cognitive impairment, psychological symptoms, and neurodegeneration. This study aimed to evaluate the effects of environmental and genetic factors on the molecular clock and to establish a link between circadian rhythm disturbance and AD. We investigated the pathological effects of chronic sleep deprivation (CSD) in the APPswe /PS1ΔE9 transgenic mice and their wild-type (WT) littermates for 2 months and evaluated the expression levels of clock genes in the circadian rhythm-related nuclei. Our results showed that CSD impaired learning and memory, and further exaggerated disease progression in the AD mice. Furthermore, CSD caused abnormal expression of Bmal1, Clock, and Cry1 in the circadian rhythm-related nuclei of experimental mice, and these changes are more significant in AD mice. Abnormal expression of clock genes in AD mice suggested that the expression of clock genes is affected by APP/PS1 mutations. In addition, abnormal tau phosphorylation was found in the retrosplenial cortex, which was co-located with the alteration of BMAL1 protein level. Moreover, the level of tyrosine hydroxylase in the locus coeruleus of AD and WT mice was significantly increased after CSD. There may be a potential link between the molecular clock, Aβ pathology, tauopathy, and the noradrenergic system. The results of this study provided new insights into the potential link between the disruption of circadian rhythm and the development of AD.
Access this article: https://doi-org.proxy.library.carleton.ca/10.1111/bpa.13028
Title: Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: An Update
Authors: Feng Zhang, Long Niu, Xinyao Liu, Yufei Liu, Song Li, Huan Yu, Weidong Le
Rapid eye movement sleep behavior disorder (RBD) is a sleep behavior disorder characterized by abnormal behaviors and loss of muscle atonia during rapid eye movement (REM) sleep. RBD is generally considered to be associated with synucleinopathies, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), and usually precedes years before the first symptom of these diseases. It is believed that RBD predicts the neurodegeneration in synucleinopathy. However, increasing evidences have shown that RBD is also found in non-synucleinopathy neurodegenerative diseases, including Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), etc. Sleep disturbance such as RBD may be an early sign of neurodegeneration in these diseases, and also serve as an assessment of cognitive impairments. In this review, we updated the clinical characteristics, diagnosis, and possible mechanisms of RBD in neurogenerative diseases. A better understanding of RBD in these neurogenerative diseases will provide biomarkers and novel therapeutics for the early diagnosis and treatment of the diseases.
Access this article: https://doi-org.proxy.library.carleton.ca/10.14336/ad.2019.0324
Title: Alteration in sleep architecture and electroencephalogram as an early sign of Alzheimer's disease preceding the disease pathology and cognitive decline. Alzheimer's & Dementia
Authors: Feng Zhang, Rujia Zhong, Song Li, Zhenfa Fu, Renfei Wang, Tianxiao Wang, Zhili Huang, Weidong Le
Type: Theoretical Article
Objective: The present work aims to evaluate the significance of sleep disturbance and electroencephalogram (EEG) alteration in the early stage of Alzheimer's disease (AD).
Background and rationale: Sleep disturbance is common in patients with AD. It is not known if it can occur at the early stage of AD and if EEG recording may help identify the early sign of the disease.
Historical evolution: Sleep disturbance in AD has generally been considered as late consequence of the neurodegenerative process. A growing body of evidence has suggested that the sleep disturbance may occur at the early stage of AD.
Updated hypothesis: Based on the previous epidemiologic studies and our recent findings, we propose that sleep disturbance may play an important role in the development of AD. Sleep EEG changes may serve as a valuable early sign for AD in the prepathological stage.
Early experimental data: Our data suggested that AβPPswe/PS1ΔE9 transgenic AD mice at preplaque stage (3 and 4 months of age) exhibited different profile of sleep architecture and sleep EEG, which preceded the cognitive deficit and AD neuropathology.
Future experiments and validation studies: Future experiments should focus on sleep EEG changes in patients with mild cognitive impairment and early stage of AD. Follow-up studies in high-risk population of the elderly are equally important. In addition, the exact molecular mechanism underlying the sleep disturbance should be thoroughly investigated.
Major challenges for the hypothesis: Studies on human participants with early stage of AD, especially the follow-up studies on the presymptomatic elderly in a large population, are difficult and time-consuming.
Linkage to other major theories: Our hypothesis may link previous theories to establish a bidirectional relationship between sleep disorders and AD, which may finally form a new schematic mechanism to understand the disease pathogenesis and disease progression.
Access this article: https://doi-org.proxy.library.carleton.ca/10.1016/j.jalz.2018.12.004
Title: The missing link between sleep disorders and age-related dementia: recent evidence and plausible mechanisms
Authors: Feng Zhang, Rujia Zhong, Song Li, Raymond Chuen-Chung Chang, Weidong Le
Sleep disorders are among the most common clinical problems and possess a significant concern for the geriatric population. More importantly, while around 40% of elderly adults have sleep-related complaints, sleep disorders are more frequently associated with co-morbidities including age-related neurodegenerative diseases and mild cognitive impairment. Recently, increasing evidence has indicated that disturbed sleep may not only serve as the consequence of brain atrophy, but also contribute to the pathogenesis of dementia and, therefore, significantly increase dementia risk. Since the current therapeutic interventions lack efficacies to prevent, delay or reverse the pathological progress of dementia, a better understanding of underlying mechanisms by which sleep disorders interact with the pathogenesis of dementia will provide possible targets for the prevention and treatment of dementia. In this review, we briefly describe the physiological roles of sleep in learning/memory, and specifically update the recent research evidence demonstrating the association between sleep disorders and dementia. Plausible mechanisms are further discussed. Moreover, we also evaluate the possibility of sleep therapy as a potential intervention for dementia.
Access this article: https://doi-org.proxy.library.carleton.ca/10.1007/s00702-017-1696-9
Title: Chronic Sleep Deprivation Exacerbates Learning-Memory Disability and Alzheimer's Disease-Like Pathologies in AβPP(swe)/PS1(ΔE9) Mice
Authors: Hongyan Qiu, Rujia Zhong, Hui Liu, Feng Zhang, Song Li, Weidong Le
Type: Original Article
Recently, there is an increasing concern over the association between sleep disorders and Alzheimer’s disease (AD). Clinical observations have reported that chronic sleep deprivation (SD) may serve as a risk factor for AD. However, the pathological evidence for this assumption is still lacking. In the present study, we examined the potential impacts of chronic SD on learning-memory and AD-related pathologies in AβPPswe/PS1 ΔE9 transgenic (TG) mice and their wild-type (WT) littermates. Results indicated that mice (both TG and WT) exposed to 2-month SD showed an altered amyloid-β protein precursor processing, an elevated level of phosphorylated tau protein, and impaired cognitive performance as compared to non-sleep deprivation (NSD) controls. Moreover, the SD-treated TG mice exhibited more amyloid-β1-42 production and developed more senile plaques in the cortex and hippocampus than NSD-treated TG mice. In addition, SD caused a striking neuronal mitochondrial damage, caspase cascade activation, and neuronal apoptosis in the hippocampus of both TG and WT mice. More importantly, all these behavioral, neuropathological, and biochemical changes induced by chronic SD were long lasting and were irreversible during a 3-month normal housing condition. Collectively, these results indicate that chronic SD impairs learning and memory, exacerbates AD pathologies, and aggravates the mitochondria-mediated neuronal apoptosis in a long-lasting manner. Our findings provide important experimental evidence to prove that chronic SD is a risk factor for AD.
Access this article: https://doi-org.proxy.library.carleton.ca/10.3233/jad-150774