Anatomical and functional phenotyping of mice models of Alzheimer's disease by MR microscopy

Helene Benveniste, Yu Ma, Jasbeer Dhawan, Andrew Gifford, S. David Smith, Igor Feinstein, Congwu Du, Samuel C. Grant, Patrick R. Hof

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

32 Scopus citations

Abstract

The wide variety of transgenic mouse models of Alzheimer's disease (AD) reflects the search for specific genes that influence AD pathology and the drive to create a clinically relevant animal model. An ideal AD mouse model must display hallmark AD pathology such as amyloid plaques, neurofibrillary tangles, reactive gliosis, dystrophic neurites, neuron and synapse loss, and brain atrophy and in parallel behaviorally mimic the cognitive decline observed in humans. Magnetic resonance (MR) microscopy (MRM) can detect amyloid plaque load, development of brain atrophy, and acute neurodegeneration. MRM examples of AD pathology will be presented and discussed. What has lagged behind in preclinical research using transgenic AD mouse models is functional phenotyping of the brain; in other words, the ability to correlate a specific genotype with potential aberrant brain activation patterns. This lack of information is caused by the technical challenges involved in performing functional MRI (fMRI) in mice including the effects of anesthetic agents and the lack of relevant "cognitive" paradigms. An alternative approach to classical fMRI using external stimuli as triggers of brain activation in rodents is to electrically or pharmacologically stimulate regions directly while simultaneously locally tracking the activated interconnected regions of rodents using, for example, the manganese-enhanced MRI (MEMRI) technique. Finally, transgenic mouse models, MRM, and future AD research would be strengthened by the ability to screen for AD-like pathology in other non-AD transgenic mouse models. For example, molecular biologists may focus on cardiac or pulmonary pathologies in transgenic mice models and as an incidental finding discover behavioral AD phenotypes. We will present MRM data of brain and cardiac phenotyping in transgenic mouse models with behavioral deficits.

Original languageEnglish
Title of host publicationImaging and the Aging Brain
PublisherBlackwell Publishing Inc.
Pages12-29
Number of pages18
ISBN (Print)1573316598, 9781573316590
DOIs
StatePublished - Feb 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1097
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Alzheimer's disease
  • Imaging
  • MR microscopy
  • Mice
  • Model
  • Phenotyping

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