2004-2005
Harvey, Danielle J., Ph.D.
Jones, Edwards G., M.D. Ph.D

PI:
Harvey, Danielle J., Ph.D.

Investigators:
Harvey, Danielle J., Ph.D.

Title:
A Spatial Decomposition of White Matter Hyperintensities

Description:
The proposed research in this pilot study will develop data reduction methods to better capture information about dementia contained in structural magnetic resonance images (MRI).  These images comprise a very complex data set in which measures are available at each of thousands of volume elements or voxels.  In addition to large numbers of observations per image, these data are structurally and spatially organized and are likely to be highly correlated, at least within regions or local areas of the brain.  One measure of disease captured in an image is that of white matter hyperintensities (WMH). The most common data analytic strategy is to reduce the WMH data to a single number summary, such as the volume of WMH in the entire brain or in specific regions of the brain.  However, these summaries ignore the continuous measure of intensity level and also the spatial relationship of neighboring voxels or voxels near important structures in the brain.  Therefore, it is desirable to develop alternative numerical summaries that include both level and location, that make statistical and biological sense, that capture a significant portion of the between-person variability, and that can be applied in a practical setting.  The specific aims of this research are:

1. To develop an orthogonal decomposition of the WMH that accounts for the spatial structure of the brain and that is biologically plausible and algebraically sensible.
2. To determine if this decomposition accounts for a significant amount of between-person variation in the distribution of WMH using simulated imaging data.
3. To investigate the distribution of WMH in normal controls and cognitively impaired subjects by using the decomposition to test a hypothesis that with increasing total WMH volume, the maximal average distance of the WMH from the ventricles increases.

 

PI:
Jones, Edwards G., M.D. Ph.D

Investigators:
Jones, Edwards G.
Murray, Karl, D

Title:
Molecular Targets of Alzheimer’s Disease

Description: Pathological alterations in Alzheimer’s disease (AD) occur in multiple brain areas, including temporal and parietal lobes, regions of frontal cortex and the cingulate cortex. While most attention has focused on those areas involved in memory consolidation, for example the hippocampus, other cortical areas have been less well studied. For the purpose of this pilot project, therefore, we will concentrate on cingulate cortex, a well known target of AD pathology, whose molecular neuropathology has still to be conclusively determined. Developing these techniques for cingulate cortex will allow us in the future to broaden our scope to other neocortical areas.We will catalogue dysregulated gene expression in single neurons exhibiting neurofibrillary tangles (NFT) or senile plaque deposits from cingulate cortex of brains affected by AD. Using Thioflavin S or Congo Red histology to identify NFTs and Ab deposits, individual neurons will be isolated by Laser Capture Microdissection (LCM). Total RNA from each cell will be subjected to multiple rounds of T7 DNA-dependent RNA polymerase mediated amplification, followed by Affymetrix GeneChip analysis. Similarly processed non-affected neurons in AD brain and neurons from non-AD brain will be compared for determining disease related gene changes.