Treatment effects in a transgenic mouse model of alzheimer's disease: A magnetic resonance spectroscopy study after passive immunization

M. Marjańska, S. D. Weigand, G. Preboske, T. M. Wengenack, R. Chamberlain, G. L. Curran, J. F. Poduslo, M. Garwood, D. Kobayashi, J. C. Lin, C. R. Jack

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Despite the enormous public health impact of Alzheimer's disease (AD), no disease-modifying treatment has yet been proven to be efficacious in humans. A rate-limiting step in the discovery of potential therapies for humans is the absence of efficient non-invasive methods of evaluating drugs in animal models of disease. Magnetic resonance spectroscopy (MRS) provides a non-invasive way to evaluate the animals at baseline, at the end of treatment, and serially to better understand treatment effects. In this study, MRS was assessed as potential outcome measure for detecting disease modification in a transgenic mouse model of AD. Passive immunization with two different antibodies, which have been previously shown to reduce plaque accumulation in transgenic AD mice, was used as intervention. Treatment effects were detected by MRS, and the most striking finding was attenuation of myo-inositol (mIns) increases in APP-PS1 mice with both treatments. Additionally, a dose-dependent effect was observed with one of the treatments for mIns. MRS appears to be a valid in vivo measure of anti-Aβ therapeutic efficacy in pre-clinical studies. Because it is noninvasive, and can detect treatment effects, use of MRS-based endpoints could substantially accelerate drug discovery.

Original languageEnglish (US)
Pages (from-to)94-100
Number of pages7
JournalNeuroscience
Volume259
DOIs
StatePublished - Feb 14 2014

Bibliographical note

Funding Information:
The authors, except for Dione Kobayashi and John C. Lin, declare no competing financial interest. Dione Kobayashi and John C. Lin are employees of Rinat, Pfizer Inc. This work was supported by Pfizer-Rinat , NIH grants: BTRC P41 RR008079 , P41 EB015894 , P30 NS057091 , RO1 AG011378 , and the W.M. Keck Foundation. The authors would like to thank James Kupiec and Jaume Pons for helpful discussions and for initiating research support; Dawn M. Gregor for mouse breeding and genotypic; Angela L. Styczynski Snyder, Nathaniel J. Powell and Angela Polk for data acquisition; Christine O’Brien for animal care; Karin Wallace and Kelly Bales for brain homogenate assay support; Danielle Pappas for plasma drug level assays.

Keywords

  • MRS
  • Myo-inositol
  • N-acetylaspartate
  • Treatment detection

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