The sleep–wake Cycle and Alzheimer’s Disease: What do We know?

Lim, Miranda M.; Gerstner, Jason R.; Holtzman, David M.

doi:10.2217/nmt.14.33

Cited by 131 publications

(106 citation statements)

References 105 publications

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“…Depression as the most pronounced clinical symptom is considered as a risk factor for neurodegeneration (Donovan et al, 2015). AD patients also typically show sleep fragmentation with frequent awakenings during the night, and a propensity to sleep during the daytime (Ancoli-Israel et al, 1994; Lim et al, 2014). Recent animal studies confirmed how early occurence of AD pathology in serotonergic nuclei leads to wake-sleep cycle disturbances (Sterniczuk et al, 2010; Roh et al, 2012).…”

Section: Chemical Neuroanatomy Of the Monoaminergic Systemsmentioning

confidence: 99%

“…In fact, recent data showed that plaque formation in the brain of the APPswe/PS1ΔE9 mouse model of AD causes the deterioration of the sleep-wake cycle and loss of diurnal fluctuation of Aβ measured in the interstitial fluid (Roh et al, 2012). In addition to the effect that accumulated Aβ causes sleep deprivation, it has been shown that sleep deprivation leads to the inadequate clearance of Aβ (Roh et al, 2012; Ju et al, 2013; Lim et al, 2014; Šimić et al, 2014), contributing to more Aβ accumulation and creating a vicious circle. Besides Aβ release from raphe projection axons (Braak and Del Tredici, 2013), accumulation of Aβ due to sleep deprivation may also add to the pathology of raphe and other brainstem nuclei, particularly in the ‘pre-tangle’ stage.…”

Section: Monoaminergic Systems In Admentioning

confidence: 99%

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Monoaminergic neuropathology in Alzheimer’s disease

Šimić

Leko

Wray³

et al. 2017

Progress in Neurobiology

230

142

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None of the proposed mechanisms of Alzheimer’s disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5–20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid β as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD.

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Section: Chemical Neuroanatomy Of the Monoaminergic Systemsmentioning

confidence: 99%

Section: Monoaminergic Systems In Admentioning

confidence: 99%

Monoaminergic neuropathology in Alzheimer’s disease

Šimić

Leko

Wray³

et al. 2017

Progress in Neurobiology

230

142

View full text Add to dashboard Cite

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“…3b). Disruptions can also be caused by social or environmental factors, such as shift work or jet lag, or by disease states that involve circadian disruption including Parkinson's and Alzheimer's disease (Karatsoreos 2014;Lim et al 2014;Ondo 2014;Sterniczuk et al 2014). As such, circadian problems are often a marker of a number of diseases.…”

Section: Amplitude Of Scn Oscillationmentioning

confidence: 99%

Circadian Insights into Motivated Behavior

Antle

Silver

2015

Current Topics in Behavioral Neurosciences

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For an organism to be successful in an evolutionary sense, it and its offspring must survive. Such survival depends on satisfying a number of needs that are driven by motivated behaviors, such as eating, sleeping, and mating. An individual can usually only pursue one motivated behavior at a time. The circadian system provides temporal structure to the organism's 24 hour day, partitioning specific behaviors to particular times of the day. The circadian system also allows anticipation of opportunities to engage in motivated behaviors that occur at predictable times of the day. Such anticipation enhances fitness by ensuring that the organism is physiologically ready to make use of a time-limited resource as soon as it becomes available. This could include activation of the sympathetic nervous system to transition from sleep to wake, or to engage in mating, or to activate of the parasympathetic nervous system to facilitate transitions to sleep, or to prepare the body to digest a meal. In addition to enabling temporal partitioning of motivated behaviors, the circadian system may also regulate the amplitude of the drive state motivating the behavior. For example, the circadian clock modulates not only when it is time to eat, but also how hungry we are. In this chapter we explore the physiology of our circadian clock and its involvement in a number of motivated behaviors such as sleeping, eating, exercise, sexual behavior, and maternal behavior. We also examine ways in which dysfunction of circadian timing can contribute to disease states, particularly in psychiatric conditions that include adherent motivational states.

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“…The primary risk factors for AD include advancing age [27][28][29], nutritional patterns characterized by low intake of plant-derived foods [30], together with metabolic syndrome-related dysfunctions (e.g., cardiovascular disease and diabetes) [8,31], low socioeconomic status and a low level of educational attainment [32][33][34], low level of daily physical activity [35,36], and low cognitive training [37]. Additionally, sleep disorders [38][39][40], known to positively correlate to early A␤ deposition [41,42], exposure to air pollution [43], smoking [44], and the intake of metals (e.g. aluminum [45], dietary copper [46], and manganese [47]) have been described as possible risk factors.…”

Section: The Population and Individual Levels: Epidemiological Studiementioning

confidence: 99%

A Human-Based Integrated Framework forAlzheimer’s Disease Research

Pistollato

Cavanaugh

Chandrasekera

2015

JAD

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Abstract. Animal models of Alzheimer's disease (AD) have been extensively utilized for decades in an effort to elucidate the pathophysiological mechanisms of this disease and to test novel therapeutic approaches. However, research success has not effectively translated into therapeutic success for human patients. This translational failure is partially due to the overuse of animal models that cannot accurately recapitulate human AD etiopathogenesis or drug responses and the inadequate use of human-relevant research methods. Here, we propose how to mitigate this translational barrier by employing human-based methods to elucidate disease processes occurring at multiple levels of complexity, accounting for gene and protein expression and the impact of disease at the cellular, tissue/organ, individual, and population levels. In particular, novel human-based cellular and computational models, together with epidemiological and clinical studies, represent the ideal tools to facilitate human-relevant data acquisition, in the effort to better elucidate AD pathogenesis in a human-based setting and design more effective treatments and preventive strategies. Our analysis indicates that a paradigm shift toward human-based, rather than animal-based research is required in the face of the ever-increasing prevalence of AD in the 21st century.

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The sleep–wake Cycle and Alzheimer’s Disease: What do We know?

Cited by 131 publications

References 105 publications

Monoaminergic neuropathology in Alzheimer’s disease

Monoaminergic neuropathology in Alzheimer’s disease

Circadian Insights into Motivated Behavior

A Human-Based Integrated Framework forAlzheimer’s Disease Research

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