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Nat Rev Neurol. 2015 Aug;11(8):457-70. doi: 10.1038/nrneurol.2015.119. Epub 2015 Jul 21.

Clearance systems in the brain-implications for Alzheimer disease.

Author information

1
New York University School of Medicine, 660 First Avenue, New York, NY 10016, USA.
2
University of Southampton, Faculty of Medicine, Institute for Life Sciences, Southampton General Hospital, Southampton Hampshire, SO16 6YD, UK.
3
New York University School of Medicine, 145 East 32nd Street, New York, NY 10016, USA.
4
Zilkha Neurogenetic Institute at Keck School of Medicine of University of Southern California, 1501 San Pablo Street Los Angeles, CA 90089, USA.
5
The Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden.
6
Université Paris-Descartes, 12 Rue de l'École de Médecine, 75006 Paris, France.

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.

PMID:
26195256
PMCID:
PMC4694579
DOI:
10.1038/nrneurol.2015.119
[Indexed for MEDLINE]
Free PMC Article

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