Aberrant waste disposal in neurodegeneration: why improved sleep could be the solution

•Glymphatic clearance is an important feature of normal brain function.•Slow-wave sleep governs the optimal state of brain clearance.•Restoring sleep function could slow the process of neurodegeneration. Sleep takes up a large percentage of our lives and the full functions of this state are still no...

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Published inCerebral circulation - cognition and behavior Vol. 2; p. 100025
Main Author Wafford, Keith A.
Format Journal Article
LanguageEnglish
Published Elsevier B.V 01.01.2021
Elsevier
Subjects
Alzheimer's disease
Amyloid
Aquaporin-4
Astrocyte
Clearance
Glymphatic
Slow-wave sleep
Slow-wave sleep
MRI
NREM
AQP4
Clearance
iNPH
Aβ
CSF
Amyloid
BOLD
OSA
SWA
Alzheimer's disease
ISF
EMG
CAA
Glymphatic
EEG
Astrocyte
SWS
MCI
Aquaporin-4
NOS
REM
PET
Online AccessGet full text
ISSN2666-2450
2666-2450
DOI10.1016/j.cccb.2021.100025

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Abstract •Glymphatic clearance is an important feature of normal brain function.•Slow-wave sleep governs the optimal state of brain clearance.•Restoring sleep function could slow the process of neurodegeneration. Sleep takes up a large percentage of our lives and the full functions of this state are still not understood. However, over the last 10 years a new and important function has emerged as a mediator of brain clearance. Removal of toxic metabolites and proteins from the brain parenchyma generated during waking activity and high levels of synaptic processing is critical to normal brain function and only enabled during deep sleep. Understanding of this process is revealing how impaired sleep contributes an important and likely causative role in the accumulation and aggregation of aberrant proteins such as β-amyloid and phosphorylated tau, as well as inflammation and neuronal damage. We are also beginning to understand how brain slow-wave activity interacts with vascular function allowing the flow of CSF and interstitial fluid to drain into the body's lymphatic system. New methodology is enabling visualization of this process in both animals and humans and is revealing how these processes break down during ageing and disease. With this understanding we can begin to envisage novel therapeutic approaches to the treatment of neurodegeneration, and how reversing sleep impairment in the correct manner may provide a way to slow these processes and improve brain function.
AbstractList Sleep takes up a large percentage of our lives and the full functions of this state are still not understood. However, over the last 10 years a new and important function has emerged as a mediator of brain clearance. Removal of toxic metabolites and proteins from the brain parenchyma generated during waking activity and high levels of synaptic processing is critical to normal brain function and only enabled during deep sleep. Understanding of this process is revealing how impaired sleep contributes an important and likely causative role in the accumulation and aggregation of aberrant proteins such as β-amyloid and phosphorylated tau, as well as inflammation and neuronal damage. We are also beginning to understand how brain slow-wave activity interacts with vascular function allowing the flow of CSF and interstitial fluid to drain into the body's lymphatic system. New methodology is enabling visualization of this process in both animals and humans and is revealing how these processes break down during ageing and disease. With this understanding we can begin to envisage novel therapeutic approaches to the treatment of neurodegeneration, and how reversing sleep impairment in the correct manner may provide a way to slow these processes and improve brain function.Sleep takes up a large percentage of our lives and the full functions of this state are still not understood. However, over the last 10 years a new and important function has emerged as a mediator of brain clearance. Removal of toxic metabolites and proteins from the brain parenchyma generated during waking activity and high levels of synaptic processing is critical to normal brain function and only enabled during deep sleep. Understanding of this process is revealing how impaired sleep contributes an important and likely causative role in the accumulation and aggregation of aberrant proteins such as β-amyloid and phosphorylated tau, as well as inflammation and neuronal damage. We are also beginning to understand how brain slow-wave activity interacts with vascular function allowing the flow of CSF and interstitial fluid to drain into the body's lymphatic system. New methodology is enabling visualization of this process in both animals and humans and is revealing how these processes break down during ageing and disease. With this understanding we can begin to envisage novel therapeutic approaches to the treatment of neurodegeneration, and how reversing sleep impairment in the correct manner may provide a way to slow these processes and improve brain function.
• Glymphatic clearance is an important feature of normal brain function. • Slow-wave sleep governs the optimal state of brain clearance. • Restoring sleep function could slow the process of neurodegeneration. Sleep takes up a large percentage of our lives and the full functions of this state are still not understood. However, over the last 10 years a new and important function has emerged as a mediator of brain clearance. Removal of toxic metabolites and proteins from the brain parenchyma generated during waking activity and high levels of synaptic processing is critical to normal brain function and only enabled during deep sleep. Understanding of this process is revealing how impaired sleep contributes an important and likely causative role in the accumulation and aggregation of aberrant proteins such as β-amyloid and phosphorylated tau, as well as inflammation and neuronal damage. We are also beginning to understand how brain slow-wave activity interacts with vascular function allowing the flow of CSF and interstitial fluid to drain into the body's lymphatic system. New methodology is enabling visualization of this process in both animals and humans and is revealing how these processes break down during ageing and disease. With this understanding we can begin to envisage novel therapeutic approaches to the treatment of neurodegeneration, and how reversing sleep impairment in the correct manner may provide a way to slow these processes and improve brain function.
•Glymphatic clearance is an important feature of normal brain function.•Slow-wave sleep governs the optimal state of brain clearance.•Restoring sleep function could slow the process of neurodegeneration. Sleep takes up a large percentage of our lives and the full functions of this state are still not understood. However, over the last 10 years a new and important function has emerged as a mediator of brain clearance. Removal of toxic metabolites and proteins from the brain parenchyma generated during waking activity and high levels of synaptic processing is critical to normal brain function and only enabled during deep sleep. Understanding of this process is revealing how impaired sleep contributes an important and likely causative role in the accumulation and aggregation of aberrant proteins such as β-amyloid and phosphorylated tau, as well as inflammation and neuronal damage. We are also beginning to understand how brain slow-wave activity interacts with vascular function allowing the flow of CSF and interstitial fluid to drain into the body's lymphatic system. New methodology is enabling visualization of this process in both animals and humans and is revealing how these processes break down during ageing and disease. With this understanding we can begin to envisage novel therapeutic approaches to the treatment of neurodegeneration, and how reversing sleep impairment in the correct manner may provide a way to slow these processes and improve brain function.
Sleep takes up a large percentage of our lives and the full functions of this state are still not understood. However, over the last 10 years a new and important function has emerged as a mediator of brain clearance. Removal of toxic metabolites and proteins from the brain parenchyma generated during waking activity and high levels of synaptic processing is critical to normal brain function and only enabled during deep sleep. Understanding of this process is revealing how impaired sleep contributes an important and likely causative role in the accumulation and aggregation of aberrant proteins such as β-amyloid and phosphorylated tau, as well as inflammation and neuronal damage. We are also beginning to understand how brain slow-wave activity interacts with vascular function allowing the flow of CSF and interstitial fluid to drain into the body's lymphatic system. New methodology is enabling visualization of this process in both animals and humans and is revealing how these processes break down during ageing and disease. With this understanding we can begin to envisage novel therapeutic approaches to the treatment of neurodegeneration, and how reversing sleep impairment in the correct manner may provide a way to slow these processes and improve brain function.
ArticleNumber 100025
Author Wafford, Keith A.
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  email: kwafford@slowavetx.co.uk
  organization: Slowave Therapeutics Ltd, 113 York Road, Woking GU22 7XR, UK
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Keywords Slow-wave sleep
MRI
NREM
AQP4
Clearance
iNPH
Aβ
CSF
Amyloid
BOLD
OSA
SWA
Alzheimer's disease
ISF
EMG
CAA
Glymphatic
EEG
Astrocyte
SWS
MCI
Aquaporin-4
NOS
REM
PET
Language English
License This is an open access article under the CC BY-NC-ND license.
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Snippet •Glymphatic clearance is an important feature of normal brain function.•Slow-wave sleep governs the optimal state of brain clearance.•Restoring sleep function...
Sleep takes up a large percentage of our lives and the full functions of this state are still not understood. However, over the last 10 years a new and...
• Glymphatic clearance is an important feature of normal brain function. • Slow-wave sleep governs the optimal state of brain clearance. • Restoring sleep...
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SubjectTerms Alzheimer's disease
Amyloid
Aquaporin-4
Astrocyte
Clearance
Glymphatic
Slow-wave sleep
Title Aberrant waste disposal in neurodegeneration: why improved sleep could be the solution
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