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Remote sites of structural atrophy predict later amyloid formation in a mouse model of Alzheimer's disease.

Magnetic resonance (MR) imaging can provide a longitudinal view of neurological disease through repeated imaging of patients at successive stages of impairment. Until recently, the difficulty of manual delineation has limited volumetric analyses of MR data sets to a few select regions and a small number of subjects. Increased throughput offered by faster imaging methods, automated segmentation, and deformation-based morphometry have recently been applied to overcome this limitation with mouse models of neurological conditions. We use automated analyses to produce an unbiased view of volumetric changes in a transgenic mouse model for Alzheimer's disease (AD) at two points in the progression of disease: immediately before and shortly after the onset of amyloid formation. In addition to the cortex and hippocampus, where atrophy has been well documented in AD patients, we identify volumetric losses in the pons and substantia nigra where neurodegeneration has not been carefully examined. We find that deficits in cortical volume precede amyloid formation in this mouse model, similar to presymptomatic atrophy seen in patients with familial AD. Unexpectedly, volumetric losses identified by MR outside of the forebrain predict locations of future amyloid formation, such as the inferior colliculus and spinal nuclei, which develop pathology at very late stages of disease. Our work provides proof-of-principle that MR microscopy can expand our view of AD by offering a complete and unbiased examination of volumetric changes that guide us in revisiting the canonical neuropathology.

Pubmed ID: 20035883


  • Badea A
  • Johnson GA
  • Jankowsky JL



Publication Data

April 1, 2010

Associated Grants

  • Agency: NIH HHS, Id: DP2 OD001734
  • Agency: NIH HHS, Id: DP2 OD001734
  • Agency: NIA NIH HHS, Id: K01 AG026144
  • Agency: NIA NIH HHS, Id: K01 AG026144-05
  • Agency: NIA NIH HHS, Id: K01-AG026144
  • Agency: NCRR NIH HHS, Id: P41 RR005959
  • Agency: NCRR NIH HHS, Id: P41 RR005959-20
  • Agency: NCRR NIH HHS, Id: P41 RR005959-20S1
  • Agency: NCRR NIH HHS, Id: P41-RR005959
  • Agency: NCI NIH HHS, Id: U24 CA092656
  • Agency: NCI NIH HHS, Id: U24 CA092656-09
  • Agency: NCRR NIH HHS, Id: U24 RR021760
  • Agency: NCRR NIH HHS, Id: U24 RR021760
  • Agency: NCRR NIH HHS, Id: U24 RR021760-05

Mesh Terms

  • Alzheimer Disease
  • Amyloid
  • Animals
  • Atrophy
  • Brain
  • Disease Models, Animal
  • Female
  • Image Interpretation, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Transgenic
  • Plaque, Amyloid