title: Clearance systems in the brain-implications for Alzheimer disease.
abstract: Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.
authors.affiliation: New York University School of Medicine, 660 First Avenue, New York, NY 10016, USA.
authors.forename: Jenna M
authors.initials: JM
authors.lastname: Tarasoff-Conway
authors.affiliation: University of Southampton, Faculty of Medicine, Institute for Life Sciences, Southampton General Hospital, Southampton Hampshire, SO16 6YD, UK.
authors.forename: Roxana O
authors.initials: RO
authors.lastname: Carare
authors.affiliation: New York University School of Medicine, 145 East 32nd Street, New York, NY 10016, USA.
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Osorio
authors.affiliation: New York University School of Medicine, 145 East 32nd Street, New York, NY 10016, USA.
authors.forename: Lidia
authors.initials: L
authors.lastname: Glodzik
authors.affiliation: New York University School of Medicine, 145 East 32nd Street, New York, NY 10016, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Butler
authors.affiliation: New York University School of Medicine, 660 First Avenue, New York, NY 10016, USA.
authors.forename: Els
authors.initials: E
authors.lastname: Fieremans
authors.affiliation: New York University School of Medicine, 660 First Avenue, New York, NY 10016, USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Axel
authors.affiliation: New York University School of Medicine, 145 East 32nd Street, New York, NY 10016, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Rusinek
authors.affiliation: New York University School of Medicine, 660 First Avenue, New York, NY 10016, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Nicholson
authors.affiliation: Zilkha Neurogenetic Institute at Keck School of Medicine of University of Southern California, 1501 San Pablo Street Los Angeles, CA 90089, USA.
authors.forename: Berislav V
authors.initials: BV
authors.lastname: Zlokovic
authors.affiliation: New York University School of Medicine, 145 East 32nd Street, New York, NY 10016, USA.
authors.forename: Blas
authors.initials: B
authors.lastname: Frangione
authors.affiliation: The Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Université Paris-Descartes, 12 Rue de l'École de Médecine, 75006 Paris, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Ménard
authors.affiliation: The Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: New York University School of Medicine, 145 East 32nd Street, New York, NY 10016, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
authors.affiliation: New York University School of Medicine, 145 East 32nd Street, New York, NY 10016, USA.
authors.forename: Mony J
authors.initials: MJ
authors.lastname: de Leon
mesh_terms: D065567:Absorption, Physiological / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002556:Cerebrospinal Fluid Proteins / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D008208:Lymphatic System / Q000502:physiology; D059748:Proteolysis; D012307:Risk Factors; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; D016875:tau Proteins