Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson’s disease

Sundaram, Saranya; Hughes, Rachel; Peterson, Eric; Müller‐Oehring, Eva M.; Brontë‐Stewart, Helen; Poston, Kathleen L.; Faerman, Afik; Bhowmick, Chloe; Schulte, Tilman

doi:10.1016/j.neubiorev.2019.05.016

Cited by 106 publications

(98 citation statements)

References 163 publications

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“…However, there are many factors contributing to the vulnerability and loss of dopaminergic neurons in Parkinson's, such as oxidative stress by the normal catabolism of dopamine, glutamate toxicity, accumulation of inflammatory cytokines, and aggregation of α-synuclein protein (62). In a recently published review, Sundaram et al (63) discussed the potential involvement in the glymphatic system, circadian regulation of the sleep-wake cycle, and clearance of α-synuclein with respect to Parkinson's. Traumatic brain injury (TBI) can lead to the accumulation of α-synuclein aggregates in the midbrain dopaminergic system, contributing to the pathogenesis of Parkinson's (64).…”

Section: Discussionmentioning

confidence: 99%

Imaging the effect of the circadian light–dark cycle on the glymphatic system in awake rats

Cai

Qiao

Kulkarni

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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The glymphatic system functions in the removal of potentially harmful metabolites and proteins from the brain. Dynamic, contrast-enhanced MRI was used in fully awake rats to follow the redistribution of intraventricular contrast agent entrained to the light–dark cycle and its hypothetical relationship to the sleep–waking cycle, blood flow, and brain temperature in specific brain areas. Brain areas involved in circadian timing and sleep–wake rhythms showed the lowest redistribution of contrast agent during the light phase or time of inactivity and sleep in rats. Global brain redistribution of contrast agent was heterogeneous. The redistribution was highest along the dorsal cerebrum and lowest in the midbrain/pons and along the ventral surface of the brain. This heterogeneous redistribution of contrast agent paralleled the gradients and regional variations in brain temperatures reported in the literature for awake animals. Three-dimensional quantitative ultrashort time-to-echo contrast-enhanced imaging was used to reconstruct small, medium, and large arteries and veins in the rat brain and revealed areas of lowest redistribution overlapped with this macrovasculature. This study raises new questions and theoretical considerations of the impact of the light–dark cycle, brain temperature, and blood flow on the function of the glymphatic system.

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Section: Discussionmentioning

confidence: 99%

Imaging the effect of the circadian light–dark cycle on the glymphatic system in awake rats

Cai

Qiao

Kulkarni

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Wake-up time in our study showed negative nonlinear association with CSF a-syn, which might need further investigation, as sleep-wake rhythm disturbances were reported associated with the spread of a-syn aggregation. 27 Nonlinear associations identified here should be interpreted with caution, as it was also possible that the recommended bedtime might reflect the physiological fluctuation of CSF a-syn levels and might be influenced by multiple factors in different cohorts, for example, geographical position. 31 Besides, either excessive or insufficient sleep duration might not be recommendable.…”

Section: Discussionmentioning

confidence: 89%

“…11,12 Moreover, the circadian cycle has been reported to control the clearance of protein aggregates 26 and modulate the accumulation of a-syn. 27,28 Therefore, poor sleep quality or unsuitable sleep time points might interfere with the clearance of abnormally accumulated asyn in the brain, which may lead to a decrease in CSF total a-syn levels.…”

Section: Discussionmentioning

confidence: 99%

“…The effects of decreased sleep quality might aggravate the neurodegenerative process in PD. 27 More directly, poorer sleep quality was likely to contribute to neurodegeneration, which could be indicated by CSF asyn levels. Difficulty initiating sleep (a manifestation of insomnia) occurred more frequently in individuals with synucleinopathies compared with matched controls.…”

Section: Discussionmentioning

confidence: 99%

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Associations of sleep characteristics with alpha‐synuclein in cerebrospinal fluid in older adults

Wang

Liu

et al. 2020

Ann Clin Transl Neurol

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Objective: Sleep disorders as a preclinical symptom of synucleinopathies become more prevalent in older adults. Synucleinopathies might be caused by the abnormal aggregation of alpha-synuclein in the brain, which was indicated by alpha-synuclein levels in cerebrospinal fluid (CSF). We aimed to investigate associations of sleep characteristics with CSF alpha-synuclein in older adults. Methods: Our study recruited 536 cognitively intact individuals (aged between 40 and 90 years old) from the Chinese Alzheimer's Biomarker and Lifestyle study. Sleep behaviors were assessed by Pittsburgh Sleep Quality Index and total alpha-synuclein in CSF was measured by enzyme-linked immune-sorbent assay. We used multiple linear and non-linear regression models for research. Results: Significant non-linear associations of CSF alpha-synuclein with sleep time and duration were revealed. Individuals who went to bed and fell asleep too early or late tended to have lower CSF alpha-synuclein (reflection point for time to bed and fall asleep were 10:26 p.m. and 10:40 p.m.). Lower CSF alpha-synuclein was also observed in individuals with either excessive or insufficient sleep duration (reflection point: 7.24 hours). Besides, overall poor sleep quality (b = À0.0621; P = 0.0242), longer sleep latency (b = À0.0415; P = 0.0174) and lower sleep efficiency (b = 0.0036; P = 0.0017) showed linear associations with lower CSF alpha-synuclein. Sleep disturbances and daytime dysfunction were not significantly associated with CSF alpha-synuclein. Interpretation: Poor sleep was associated with lower levels of CSF alpha-synuclein in older adults, which may provide new insight into the prevention of synucleinopathies.

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“…This system is mainly activated during sleep [121]. Because glymphatics participate in waste clearance through exchanges with the interstitial and cerebrospinal fluid, this system can deal differently with extracellular (B-amyloid and tau protein) and intracellular (alpha-synuclein) proteins [122,123]. Thus, sleep fragmentation due to OSA could alter this homeostatic system and predispose it to protein accumulation and neurodegenerative changes.…”

Section: Pathogenesis Of Cognitive Impairment In Osamentioning

confidence: 99%

Obstructive Sleep Apnea in Neurodegenerative Disorders: Current Evidence in Support of Benefit from Sleep Apnea Treatment

Lajoie

Lafontaine

Kimoff

et al. 2020

JCM

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Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurrent upper airway obstruction during sleep resulting in intermittent hypoxemia and sleep fragmentation. Research has recently increasingly focused on the impact of OSA on the brain’s structure and function, in particular as this relates to neurodegenerative diseases. This article reviews the links between OSA and neurodegenerative disease, focusing on Parkinson’s disease, including proposed pathogenic mechanisms and current knowledge on the effects of treatment.

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Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson’s disease

Cited by 106 publications

References 163 publications

Imaging the effect of the circadian light–dark cycle on the glymphatic system in awake rats

Imaging the effect of the circadian light–dark cycle on the glymphatic system in awake rats

Associations of sleep characteristics with alpha‐synuclein in cerebrospinal fluid in older adults

Obstructive Sleep Apnea in Neurodegenerative Disorders: Current Evidence in Support of Benefit from Sleep Apnea Treatment

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