Supplemental Material for:
Remote sites of structural atrophy predict later amyloid formation in a mouse model of Alzheimer's disease
Alexandra Badea1, G. Allan Johnson1, 2, Joanna L. Jankowsky3
1Center for In Vivo Microscopy, 2Departments of Radiology, Biomedical Engineering, and Physics Duke University Medical Center, Durham, NC, 3Departments of Neuroscience, Neurology, and Neurosurgery, Baylor College of Medicine, Houston, TX
Neuroimage 50: 416-427, 2010. PMCID: PMC2823970
Magnetic resonance (MR) imaging provides 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 datasets
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 longitudinal view of volumetric changes in a transgenic mouse model
for Alzheimer's disease (AD). 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 pre-symptomatic 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
very late in disease. We further show that MR microscopy can detect amyloid
deposits shortly after they are formed, when the cortex and hippocampus are
only modestly involved in pathology. We show histology-confirmed plaques
in T2* images of fixed brains at the earliest stage of disease yet studied
by MR. Our work provides proof-of-principle that MR microscopy can expand
our view of AD, from the earliest amyloid deposits to the most remote volumetric changes.
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