Magnetic resonance imaging of Alzheimer's pathology in the brains of living transgenic mice: A new tool in Alzheimer's disease research

Clifford R. Jack, Malgorzata Marjanska, Thomas M. Wengenack, Denise A. Reyes, Geoffrey L. Curran, Joseph Lin, Gregory M. Preboske, Joseph F. Poduslo, Michael Garwood

Research output: Contribution to journalReview article

60 Scopus citations

Abstract

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Cardinal pathologic features of AD are amyloid plaques and neurofibrillary tangles, and most in the field believe that the initiating events ultimately leading to clinical AD center on disordered metabolism of amyloid beta protein. Mouse models of AD have been created by inserting one or more human mutations associated with disordered amyloid metabolism and that cause early onset familial AD into the mouse genome. Human-like amyloid plaque formation increases dramatically with age in these transgenic mice. Amyloid reduction in humans is a major therapeutic objective, and AD transgenic mice allow controlled study of this biology. Recent work has shown that amyloid plaques as small as 35 μm can be detected using in vivo magnetic resonance microimaging (MRMI) at high magnetic field (9.4 T). In addition, age-dependent changes in metabolite concentration analogous to those that have been identified in human AD patients can be detected in these transgenic mice using single-voxel 1H magnetic resonance spectroscopy (1H MRS) at high magnetic field. These MR-based techniques provide a new set of tools to the scientific community engaged in studying the biology of AD in transgenic models of the disease. For example, an obvious application is evaluating therapeutic modification of disease progression. Toward the end of this review, the authors include results from a pilot study demonstrating feasibility of using MRMI to detect therapeutic modification of plaque progression in AD transgenic mice.

Original languageEnglish (US)
Pages (from-to)38-48
Number of pages11
JournalNeuroscientist
Volume13
Issue number1
DOIs
StatePublished - Feb 1 2007

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Keywords

  • Alzheimer's disease
  • Alzheimer's disease therapy
  • H magnetic resonance spectroscopy
  • Magnetic resonance microimaging
  • Transgenic Alzheimer's mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Jack, C. R., Marjanska, M., Wengenack, T. M., Reyes, D. A., Curran, G. L., Lin, J., Preboske, G. M., Poduslo, J. F., & Garwood, M. (2007). Magnetic resonance imaging of Alzheimer's pathology in the brains of living transgenic mice: A new tool in Alzheimer's disease research. Neuroscientist, 13(1), 38-48. https://doi.org/10.1177/1073858406295610