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Monitoring of chronic γ-secretase modulator treatment by serial amyloid-PET

Molecular Psychiatry volume 20, page 1141 (2015)Cite this article

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Horizontal slices of serial β-amyloid positron emission tomography (PET) images of representative APP-Swe mice aged 12 months at baseline prior treatment (BL), as well as 4 months (FU1) and 6 months upon treatment initiation (FU2); uptake images are superimposed on a magnetic resonance imaging atlas. Treatment with the γ-secretase modulator RO5506284 (30 mg kg−1 per day) or vehicle continued until study termination. The first row depicts results for an RO5506284-treated animal with high baseline amyloid level, which turned out to be less effectively treated, as indicated by the increased PET signal at FU2. In this case, the SUVRCTX/CBL after partial volume effect correction (PVEC) increased from 1.11 at baseline to 1.12 at FU1 and 1.20 at study termination. The second row depicts results for an RO5506284-treated animal with low baseline amyloid level, which did not progress during follow-up. In this case the serial SUVRCTX/CBL with PVEC was 0.95 at baseline, 0.94 at first follow-up, and 0.91 six months after treatment initiation, suggesting good response to RO5506284 treatment. Notably, this responding animal developed a histologically verified large plaque during treatment, indicated by the hotspot in FU2-PET, whereas the surrounding brain remained nearly plaque-free. A primary effect of RO5506284 on de novo amyloidogenesis is suggested by development of only a few but rather large plaques. The third row depicts the results for an untreated animal, in which serial PET revealed a steady increase from a low baseline amyloid level. Serial SUVRCTX/CBL with PVEC increased from 0.93 at baseline to 1.09 four months and 1.18 six months later. For more information on this topic, please refer to the article by Brendel et al. on pages 1179–1187.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany

    M Brendel, C Rötzer, F-J Gildehaus, J Carlsen, P Bartenstein & A Rominger

  2. DZNE—German Center for Neurodegenerative Diseases, Munich, Germany

    A Jaworska, J Herms, H Steiner & C Haass

  3. Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, Warsaw, Poland

    A Jaworska

  4. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

    J Herms, P Bartenstein, C Haass & A Rominger

  5. Biomedical Center (BMC), Ludwig-Maximilians-University of Munich, Munich, Germany

    J Trambauer, H Steiner & C Haass

  6. Department of Psychiatry, University of Oslo, Oslo, Norway

    P Cumming

  7. Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, Switzerland

    J Bylund

  8. Roche Pharma Research and Early Development, Small Molecule Research, Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, Switzerland

    T Luebbers

  9. Roche Pharma Research and Early Development, Neuroscience Discovery, Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, Switzerland

    K Baumann

Authors
  1. M Brendel
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  2. A Jaworska
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  3. J Herms
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  4. J Trambauer
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  5. C Rötzer
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  6. F-J Gildehaus
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  7. J Carlsen
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  8. P Cumming
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  9. J Bylund
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  10. T Luebbers
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  11. P Bartenstein
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  12. H Steiner
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  13. C Haass
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  14. K Baumann
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  15. A Rominger
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Brendel, M., Jaworska, A., Herms, J. et al. Monitoring of chronic γ-secretase modulator treatment by serial amyloid-PET. Mol Psychiatry 20, 1141 (2015). https://doi.org/10.1038/mp.2015.146

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