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Connections Between Amyloid Beta and the Meningeal Lymphatics As a Possible Route for Clearance and Therapeutics.

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder causing progressive cognitive decline, memory loss, and death of neural tissue. Current research suggests a connection between bulk flow of interstitial fluid and cerebrospinal fluid across the blood-brain barrier and the recently confirmed meningeal lymphatic channels of the brain. The main symptom of interest in AD is the spontaneous aggregation of amyloid beta (Aβ) proteins resulting from increased production or lack of clearance from brain tissues. These protein aggregates manifest as plaques in the capillary and artery lumina and the neuronal and dural tissues of the brain, and are known to contribute to cerebral amyloid angiopathy and a host of other neuroinflammatory conditions. The meningeal lymphatics contain a substantial population of immune cells and also serve as a drain into the deep cervical lymph nodes. In this study we discuss the molecular mechanisms by which Aβ could gain access to meningeal lymphatic channels through the blood-brain interface, including ways in which it can be cleared to preclude aggregation and plaque deposition.

Authors+Show Affiliations

Seattle Science Foundation, Seattle, Washington.Seattle Science Foundation, Seattle, Washington.Swedish Neuroscience Institute, Swedish Medical Center, Seattle, Washington.Seattle Science Foundation, Seattle, Washington. Department of Anatomical Sciences, St. George's University, St. George's, Grenada, West Indies.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31433264

Citation

Dupont, Graham, et al. "Connections Between Amyloid Beta and the Meningeal Lymphatics as a Possible Route for Clearance and Therapeutics." Lymphatic Research and Biology, 2019.
Dupont G, Iwanaga J, Yilmaz E, et al. Connections Between Amyloid Beta and the Meningeal Lymphatics As a Possible Route for Clearance and Therapeutics. Lymphat Res Biol. 2019.
Dupont, G., Iwanaga, J., Yilmaz, E., & Tubbs, R. S. (2019). Connections Between Amyloid Beta and the Meningeal Lymphatics As a Possible Route for Clearance and Therapeutics. Lymphatic Research and Biology, doi:10.1089/lrb.2018.0079.
Dupont G, et al. Connections Between Amyloid Beta and the Meningeal Lymphatics as a Possible Route for Clearance and Therapeutics. Lymphat Res Biol. 2019 Aug 21; PubMed PMID: 31433264.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Connections Between Amyloid Beta and the Meningeal Lymphatics As a Possible Route for Clearance and Therapeutics. AU - Dupont,Graham, AU - Iwanaga,Joe, AU - Yilmaz,Emre, AU - Tubbs,R Shane, Y1 - 2019/08/21/ PY - 2019/8/22/entrez KW - Alzheimer's disease KW - amyloid beta KW - blood–brain interface KW - glymphatic system KW - meningeal lymphatics JF - Lymphatic research and biology JO - Lymphat Res Biol N2 - Alzheimer's disease (AD) is a complex neurodegenerative disorder causing progressive cognitive decline, memory loss, and death of neural tissue. Current research suggests a connection between bulk flow of interstitial fluid and cerebrospinal fluid across the blood-brain barrier and the recently confirmed meningeal lymphatic channels of the brain. The main symptom of interest in AD is the spontaneous aggregation of amyloid beta (Aβ) proteins resulting from increased production or lack of clearance from brain tissues. These protein aggregates manifest as plaques in the capillary and artery lumina and the neuronal and dural tissues of the brain, and are known to contribute to cerebral amyloid angiopathy and a host of other neuroinflammatory conditions. The meningeal lymphatics contain a substantial population of immune cells and also serve as a drain into the deep cervical lymph nodes. In this study we discuss the molecular mechanisms by which Aβ could gain access to meningeal lymphatic channels through the blood-brain interface, including ways in which it can be cleared to preclude aggregation and plaque deposition. SN - 1557-8585 UR - https://www.unboundmedicine.com/medline/citation/31433264/Connections_Between_Amyloid_Beta_and_the_Meningeal_Lymphatics_As_a_Possible_Route_for_Clearance_and_Therapeutics L2 - https://www.liebertpub.com/doi/full/10.1089/lrb.2018.0079?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -