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Acta Neuropathologica

, Volume 128, Issue 4, pp 611–614 | Cite as

Anti-Aβ antibody target engagement: a response to Siemers et al.

  • Andrew D. Watt
  • Gabriela A. N. Crespi
  • Russell A. Down
  • David B. Ascher
  • Adam Gunn
  • Keyla A. Perez
  • Catriona A. McLean
  • Victor L. Villemagne
  • Michael W. Parker
  • Kevin J. BarnhamEmail author
  • Luke A. MilesEmail author
Correspondence

We have read with interest the commentary by Siemers et al. [28] regarding our paper describing the ability of the three anti-Aβ antibodies, bapineuzumab, crenezumab and solanezumab to engage Aβ in both a synthetic and a biological setting. We appreciate the opportunity to clarify any misunderstandings and here provide a brief response to their concerns.

Siemers et al. [28] begin their commentary by stating that our findings led to the conclusion “that all three antibodies failed to engage the intended molecular targets”. This statement is wrong; as clearly stated in the abstract of our paper, “Bapineuzumab demonstrated target engagement with brain Aβ, consistent with published clinical data”. To reiterate, we reported data showing that bapineuzumab was capable of binding soluble Aβ with a low nanomolar affinity and demonstrated that the antibody could detect Aβ species in buffer and in brain homogenate and plasma from transgenic animal models of AD. Furthermore, in agreement with the...

Keywords

Brain Homogenate Transgenic Animal Model Target Engagement Cortical Homogenate Femtomolar Concentration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Conflict of interest

None.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Andrew D. Watt
    • 1
    • 2
    • 3
  • Gabriela A. N. Crespi
    • 7
  • Russell A. Down
    • 1
    • 2
    • 3
  • David B. Ascher
    • 7
  • Adam Gunn
    • 1
    • 3
  • Keyla A. Perez
    • 1
    • 3
  • Catriona A. McLean
    • 1
    • 8
  • Victor L. Villemagne
    • 1
    • 6
    • 9
  • Michael W. Parker
    • 4
    • 7
  • Kevin J. Barnham
    • 1
    • 3
    • 5
    Email author
  • Luke A. Miles
    • 4
    • 7
    Email author
  1. 1.Florey Institute of Neuroscience and Mental HealthThe University of MelbourneMelbourneAustralia
  2. 2.Department of PathologyThe University of MelbourneMelbourneAustralia
  3. 3.Neuroproteomics Platform, Bio21 Molecular Science and Biotechnology InstituteThe University of MelbourneMelbourneAustralia
  4. 4.Department of Biochemistry and Molecular BiologyThe University of MelbourneMelbourneAustralia
  5. 5.Department of Pharmacology and TherapeuticsThe University of MelbourneMelbourneAustralia
  6. 6.Department of MedicineThe University of MelbourneMelbourneAustralia
  7. 7.ACRF Rational Drug Discovery CentreSt. Vincent’s Institute of Medical ResearchFitzroyAustralia
  8. 8.Department of Anatomical PathologyThe Alfred HospitalMelbourneAustralia
  9. 9.Department of Nuclear Medicine and Centre for PETAustin HealthHeidelbergAustralia

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