title: Treatment effects in a transgenic mouse model of Alzheimer's disease: a magnetic resonance spectroscopy study after passive immunization.
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.
authors: Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: gosia@cmrr.umn.edu.
authors: M
authors: M
authors: Marjańska
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55902, USA.
authors: S D
authors: SD
authors: Weigand
authors: Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.
authors: G
authors: G
authors: Preboske
authors: Departments of Neurology, Neuroscience, and Biochemistry/Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.
authors: T M
authors: TM
authors: Wengenack
authors: Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, MN 55455, USA.
authors: R
authors: R
authors: Chamberlain
authors: Departments of Neurology, Neuroscience, and Biochemistry/Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.
authors: G L
authors: GL
authors: Curran
authors: Departments of Neurology, Neuroscience, and Biochemistry/Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.
authors: J F
authors: JF
authors: Poduslo
authors: Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, MN 55455, USA.
authors: M
authors: M
authors: Garwood
authors: Rinat, Pfizer Inc., South San Francisco, CA 94080, USA.
authors: D
authors: D
authors: Kobayashi
authors: Rinat, Pfizer Inc., South San Francisco, CA 94080, USA.
authors: J C
authors: JC
authors: Lin
authors: Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.
authors: C R
authors: CR
authors: Jack
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002794:Choline; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D007294:Inositol; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D018709:Statistics, Nonparametric
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D002794:Choline
keywords: AD; AFP; AHP; Alzheimer’s disease; CRLBs; Cramér-Rao Lower Bounds; FID; MRS; N-acetylaspartate; NAA; WT; adiabatic full-passage; adiabatic half-passage; free induction decay; mIns; magnetic resonance spectroscopy; myo-inositol; tCr; total creatine, sum of creatine and phosphocreatine; treatment detection; wild-type