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Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson’s disease
Open accessAbstract
Recent evidence has advanced our understanding of the function of sleep to include removal of neurotoxic protein aggregates via the glymphatic system. However, most research on the glymphatic system utilizes animal models, and the function of waste clearance processes in humans remains unclear. Understanding glymphatic function offers new insight into the development of neurodegenerative diseases that result from toxic protein inclusions, particularly those characterized by neuropathological sleep dysfunction, like Parkinson's disease (PD). In PD, we propose that glymphatic flow may be compromised due to the combined neurotoxic effects of alpha-synuclein protein aggregates and deteriorated dopaminergic neurons that are linked to altered REM sleep, circadian rhythms, and clock gene dysfunction. This review highlights the importance of understanding the functional role of glymphatic system disturbance in neurodegenerative disorders and the subsequent clinical and neuropathological effects on disease progression. Future research initiatives utilizing noninvasive brain imaging methods in human subjects with PD are warranted, as in vivo identification of functional biomarkers in glymphatic system functioning may improve clinical diagnosis and treatment of PD.
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“The suppressive effects of both age and amyloid-ß overexpression on glymphatic flow can be extended to other experimental rodent models of neurodegeneration; both traumatic brain injury and Parkinson’s disease are similarly linked to a sustained reduction of glymphatic fluid transport (56–58).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [58]
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Metadata
- Authors
- Sundaram, S., Hughes, R. L., Peterson, E., Müller-Oehring, E. M., Brontë-Stewart, H. M., Poston, K. L., Faerman, A., Bhowmick, C., & Schulte, T.
- Affiliations
- Palo Alto University (US)
- SRI International (US)
- Stanford Medicine (US)
- Corresponding author
- Schulte, Tilman
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 103
- Pages
- 305-315
- ISSN
- 0149-7634 (ISSN-L)
- PMC
- PMC6692229
- OpenAlex
- W2945136852
- Cited by
- 152
- References
- 175
- Citations by year
- 2026: 10 · 2025: 31 · 2024: 24 · 2023: 22 · 2022: 27 · 2021: 25 · 2020: 10 · 2019: 2
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuroscience & Biobehavioral Reviews (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism
- National Institute of Neurological Disorders and Stroke
- Topics
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- Parkinson's disease, glymphatic system, sleep, alpha-synuclein aggregates, REM sleep, circadian rhythm, clock genes, dopaminergic neurons, neurodegeneration, waste clearance, biomarkers
- MeSH terms
- Glymphatic System, Humans, Parkinson Disease, Sleep Wake Disorders, alpha-Synuclein, CLOCK Proteins
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