Decreased Clearance of CNS Amyloid-β in Alzheimer’s Disease

By K. Mawuenyega, Wendy C. Sigurdson, Vitaliy Ovod, L. Munsell, Tom Kasten, John C. Morris, K. Yarasheski, Randall J. Bateman. Science, 2010

1,806 citations recorded by the source corpus.

Alzheimer’s disease is associated with reduced β-amyloid clearance from the brain Alzheimer’s disease is hypothesized to be caused by an imbalance between β-amyloid (Aβ) production and clearance that leads to Aβ accumulation in the central nervous system (CNS). Aβ production and clearance are key targets in the development of disease-modifying therapeutic agents for Alzheimer’s disease. However, there has not been direct evidence of altered Aβ production or clearance in Alzheimer’s disease. By using metabolic labeling, we measured Aβ42 and Aβ40 production and clearance rates in the CNS of participants with Alzheimer’s disease and cognitively normal controls. Clearance rates for both Aβ42 and Aβ40 were impaired in Alzheimer’s disease compared with controls. On average, there were no differences in Aβ40 or Aβ42 production rates. Thus, the common late-onset form of Alzheimer’s disease is characterized by an overall impairment in Aβ clearance.

Subfields: Geometry and Topology, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/ff40fcdfb6e902a70b08f082542c3d0864b12221

How researchers see this paper

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

In Geometry and Topology

1. Anders M. Fjell
2. Kristine B. Walhovd
3. A. M. Dale
4. Bruce Fischl

In Physiology

1. D. Holtzman
2. D. Selkoe
3. John Hardy
4. A. Goate
5. John C. Morris
6. A. M. Dale
7. Anders M. Fjell
8. Kristine B. Walhovd

In Psychiatry and Mental health

1. John Hardy
2. D. Holtzman
3. A. Goate
4. John C. Morris
5. D. Selkoe
6. Anders M. Fjell
7. Kristine B. Walhovd
8. A. M. Dale

Citations in the corpus

• 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).”
• Alzheimer’s Disease: The Challenge of the Second Century (2011, background): “In sporadic LOAD, current evidence does not support Ab overproduction as a cause, although there is emerging evidence suggesting deficits in Ab clearance (216).”
• What is normal in normal aging? Effects of Aging, Amyloid and Alzheimer’s Disease on the Cerebral Cortex and the Hippocampus (2014, background): “…is that there is growing agreement that Ab accumulation in sporadic AD is more related to decreased clearance than increased production (DeMattos et al., 2004; Mawuenyega et al., 2010; Castellano et al., 2011), in contrast to increased Ab production seen in familial AD (Scheuner et al., 1996).”
• Human apoE isoforms differentially regulate brain amyloid-β peptide clearance (2011, neutral): “For example, using in vivo stable isotopic labeling kinetics, our group recently reported that CSF Ab clearance and not synthesis is impaired in a small cohort of late-onset AD patients, although the effect of APOE genotype was not assessed (65).”