Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Sep 13;10(9):2261.
doi: 10.3390/biomedicines10092261.

The Role of Glymphatic System in Alzheimer's and Parkinson's Disease Pathogenesis

Affiliations
Review

The Role of Glymphatic System in Alzheimer's and Parkinson's Disease Pathogenesis

Francesca R Buccellato et al. Biomedicines. .

Abstract

Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia, whilst Parkinson's disease (PD) is a neurodegenerative movement disorder. These two neurodegenerative disorders share the accumulation of toxic proteins as a pathological hallmark. The lack of definitive disease-modifying treatments for these neurogenerative diseases has led to the hypothesis of new pathogenic mechanisms to target and design new potential therapeutic approaches. The recent observation that the glymphatic system is supposed to be responsible for the movement of cerebrospinal fluid into the brain and clearance of metabolic waste has led to study its involvement in the pathogenesis of these classic proteinopathies. Aquaporin-4 (AQP4), a water channel located in the endfeet of astrocyte membrane, is considered a primary driver of the glymphatic clearance system, and defective AQP4-mediated glymphatic drainage has been linked to proteinopathies. The objective of the present review is to present the recent body of knowledge that links the glymphatic system to the pathogenesis of AD and PD disease and other lifestyle factors such as sleep deprivation and exercise that may influence glymphatic system function. We will also focus on the potential neuroimaging approaches that could identify a neuroimaging marker to detect glymphatic system changes.

Keywords: Alzheimer’s disease; Aquaporin 4; Parkinson’s disease; glymphatic system; neuroimaging.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic figure of the current model of the Glymphatic system.

References

    1. Iliff J.J., Wang M., Liao Y., Plogg B.A., Peng W., Gundersen G.A., Benveniste H., Vates G.E., Deane R., Goldman S.A., et al. A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β. Sci. Transl. Med. 2012;4:147ra111. doi: 10.1126/scitranslmed.3003748. - DOI - PMC - PubMed
    1. MacAulay N. Molecular mechanisms of brain water transport. Nat. Rev. Neurosci. 2021;22:326–344. doi: 10.1038/s41583-021-00454-8. - DOI - PubMed
    1. Hladky S.B., Barrand M.A. The glymphatic hypothesis: The theory and the evidence. Fluids Barriers CNS. 2022;19:9. doi: 10.1186/s12987-021-00282-z. - DOI - PMC - PubMed
    1. Salman M.M., Kitchen P., Iliff J.J., Bill R.M. Aquaporin 4 and glymphatic flow have central roles in brain fluid homeostasis. Nat. Rev. Neurosci. 2021;22:650–651. doi: 10.1038/s41583-021-00514-z. - DOI - PubMed
    1. Mestre H., Mori Y., Nedergaard M. The Brain’s Glymphatic System: Current Controversies. Trends Neurosci. 2020;43:458–466. doi: 10.1016/j.tins.2020.04.003. - DOI - PMC - PubMed