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Reply to: Fractional synthesis and clearance rates for amyloid β

Nature Medicine volume 17, pages 1179–1180 (2011)Cite this article

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Elbert et al. reply:

We appreciate the motivation for the theoretical model proposed by Edland et al.1 on the basis of our report in Nature Medicine2 and subsequent studies showing decreased amyloid-β (Aβ) production with pharmacologic treatment3 and decreased Aβ clearance in Alzheimer's disease4. We use 'clearance' to refer to any process that removes the measured analyte (for example, Aβ), including cellular and enzymatic degradation processes and blood-brain barrier and cerebrospinal fluid (CSF) transport mechanisms. The authors propose that clearance of labeled proteins, as measured by in vivo stable isotope–labeled kinetics (SILK), does not reflect brain processes of clearance1. Although they do not provide additional experimental data, they do propose a theoretical model to support their assertions. However, in reviewing the proposed model, we suggest the model and the assertions made are not an accurate interpretation of our data or the physiology of CSF production and clearance (for additional description, please see Supplementary Figs. 1–8). Furthermore, we are concerned that the suggestion to not measure clearance of labeled proteins will lead to less understanding of CNS protein metabolism. We suggest that the proposed model of Edland et al.1 is limited because it does not fit the experimental data, is not physiologically compatible with known CNS structure and physiology, and implements incorrect assumptions that are not supported by established isotope tracer methods. We thank Edland et al.1 for proposing their model and support the modeling of CNS Aβ generation, transport and degradation mechanisms, combined with additional experimental measures (including clearance measures) to provide major insights into the normal physiological and pathological roles of Aβ and other CNS proteins.

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References

  1. Edland, S.D. & Galasko, D.R. et al. Nat. Med. 17, 1178–1179 (2011).

    Article  CAS  Google Scholar 

  2. Bateman, R.J. et al. Nat. Med. 12, 856–861 (2006).

    Article  CAS  Google Scholar 

  3. Bateman, R.J. et al. Ann. Neurol. 66, 48–54 (2009).

    Article  CAS  Google Scholar 

  4. Mawuenyega, K.G. et al. Science 330, 1774 (2010).

    Article  CAS  Google Scholar 

  5. Wolfe, R.R. & Chinkes, D.L. Isotope Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis 2nd edn., Chapter 13 (Wiley-Liss, Hoboken, New Jersey, 2005).

    Google Scholar 

  6. Zilversmit, D.B. Am. J. Med. 29, 832–848 (1960).

    Article  CAS  Google Scholar 

  7. Holtzman, D., Bateman, R. & Kim, J. Methods for measuring the metabolism of CNS derived biomolecules in vivo. US patent application 2009/0142766 A1.

  8. Wildsmith, K.R., Han, B. & Bateman, R.J. Anal. Biochem. 395, 116–118 (2009).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA

    Donald L Elbert

  2. Department of Internal Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA

    Bruce W Patterson

  3. Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA

    Lindsay Ercole & Tammie Benzinger

  4. Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA

    Vitaliy Ovod, Tom Kasten, Kwasi Mawuenyega, John C Morris, David M Holtzman & Randall J Bateman

  5. Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

    Kevin Yarasheski

  6. Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA

    John C Morris, David M Holtzman & Randall J Bateman

  7. Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri, USA

    David M Holtzman & Randall J Bateman

Authors
  1. Donald L Elbert
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Corresponding author

Correspondence to Randall J Bateman.

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Competing interests

R.J.B. and D.M.H. are cofounders of a company (C2N Diagnostics) that has licensed a Washington University patent on the technology described in the original article.

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Elbert, D., Patterson, B., Ercole, L. et al. Reply to: Fractional synthesis and clearance rates for amyloid β. Nat Med 17, 1179–1180 (2011). https://doi.org/10.1038/nm.2496

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