Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo

By Randall J. Bateman, L. Munsell, John C. Morris, R. Swarm, K. Yarasheski, D. Holtzman. Nature Medicine, 2006

613 citations recorded by the source corpus.

Subfields: Molecular Biology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/9553ad977b96f8ae310ca40c1344d3b9e2c2399d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. D. Holtzman
2. P. Tontonoz
3. John C. Morris
4. A. Goate
5. D. Selkoe
6. John Hardy
7. N. Zelcer
8. B. de Strooper

In Neurology

1. D. Selkoe
2. John Hardy
3. D. Holtzman
4. John C. Morris
5. A. Goate

In Physiology

1. D. Holtzman
2. D. Selkoe
3. John Hardy
4. A. Goate
5. John C. Morris
6. B. de Strooper
7. E. Karran
8. Jungsu Kim

Citations in the corpus

• Alzheimer’s Disease: The Challenge of the Second Century (2011, methodology): “New methods to assess whether proposed disease-modifying agents are effectively hitting their target are now being incorporated in phase I and II trials in humans (214, 215).”
• The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics (2011, background): “The total production of amyloid-β in the human brain can be assessed by extrapolating from rodent cell culture experiments and potentially from SILK technolog”
• The amyloid hypothesis of Alzheimer's disease at 25 years (2016, background): “…B (Klunk et al, 2004); and (iii) the ability to analyze APP metabolism in healthy and diseased humans by quantifying heavy isotope-labeled Ab peptides by mass spectrometry in fresh CSF collected continuously through a lumbar intrathecal catheter (Bateman et al, 2006; Mawuenyega et al, 2010).”
• ApoE promotes the proteolytic degradation of Abeta. (2008, background): “Ab peptides are normally generated at high levels in the brain ( 8%/hour) and are cleared at an equivalent rate in both humans and mice (Bateman et al., 2006).”
• The Glymphatic System – A Beginner's Guide (2015, neutral): “3 % of total b-amyloid is cleared each hour via the CSF [103].”
• The role of microglia in amyloid clearance from the AD brain (2010, background): “…are normally generated at high levels in the brain (approximately 8% per hour) and are cleared at an equivalent rate both in humans and in mice (Bateman et al. 2006), even moderately increased production or decreased clearance of Ab eventually leads to an overall elevation of its steady state…”
• Amyloid Precursor Protein Processing and Alzheimer’s Disease (2011, background): “WHY IS THERE AGE-RELATED BRAIN Aβ ACCUMULATION Large amounts of APP are continuously metabolized to Aβ in the brain (Bateman et al. 2006).”
• Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future (2023, background): “Similar to other brain metabolites, Aβ clearance depends on different pathways including enzyme degradation, crossing the blood–brain barrier (BBB), interstitial fluid (ISF) bulk-flow and CSF absorption.(19,20) The BBB is composed of endothelial cells connected by tight junctions to form a selective”
• Human apoE isoforms differentially regulate brain amyloid-β peptide clearance (2011, positive): “FSRs of Aβ were measured in hippocampal lysates from young PDAPP/TRE mice with a method adapted from the in vivo stable isotopic labeling kinetics technique we have previously described in humans (43) (detailed Materials and Methods available in the Supplementary Material).”