Clearance systems in the brain—implications for Alzheimer disease
By Jenna M. Tarasoff-Conway, Roxana O. Carare, R. Osorio, L. Glodzik, T. Butler, Els Fieremans, Leon Axel, H. Rusinek, C. Nicholson, Berislav Zlokovic and 6 more. Nature Reviews Neurology, 2015
1,551 citations recorded by the source corpus.
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.
Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Physiology
View Paper: https://www.semanticscholar.org/paper/1e1bfc2cc5aa1504ec435036d752c038526da57c
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In Physiology
Citations in the corpus
- Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “It has been suggested that vascular damage associated with CAA disrupts vascular drainage and homeostasis in the CNS, thereby impairing Aβ clearance and aggravating AD pathogenesis [606].”
- APP mouse models for Alzheimer's disease preclinical studies (2017, neutral): “The emerging insight that AD is a multidimensional and multi-cellular process will require more integrated and complex forms of analysis (Tarasoff-Conway et al , 2015; De Strooper & Karran, 2016).”
- Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future (2023, background): “CSF absorption clearance of Aβ depends on factors including CSF production by the choroid plexus, integrity of the blood-CSF barrier, relevant transporters and CSF lymphatic absorption.(28) In AD, the structural integrity of the blood-CSF barrier is destroyed, resulting in aberrant Aβ clearance.”
- Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases (2019, positive): “The progressive deposition and aggregation of Aβ peptides in the brain are the result of an imbalance between their production and clearance, a process in which brain-resident microglia and brain-infiltrating peripheral monocytes (moMφs) are involved (134, 142).”