This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Background: The apolipoprotein E (ApoE) genotype is a significant risk factor and modulator of age of onset in Alzheimer's disease; recent studies showed an association between ApoE-e4 allele and late onset Alzheimer disease (LOAD); less is known about possible ApoE-e4 allele effects in early-onset (EOAD); here we aim to investigate the association of ApoE-e4 allele on cortical atrophy and hippocampal volumes in EOAD and LOAD patients, using cortical pattern matching (CPM) algorithms and hippocampal radial mapping (HRM).Methods: High-resolution 3D MR images of EOAD and LOAD patients of similar clinical severity will be compared to those of age- and sex-matched controls. CPM is used to identify regions where the cortical gray matter density differs in cases vs controls, and HRM to assess hippocampal volumes difference.MR images are normalized to a customized template using a 12 parameter linear transformation and 3D cortical surfaces of both hemispheres are extracted; 29 sulci are manually outlined on the lateral and medial surface of each hemisphere, and additional 3D lines are drawn to delimit interhemispheric gyral limits. A population specific templates is created averaging the traced sulci among subjects, and the sulci are used as landmarks to warp each subject's anatomy to the template. Original MR images are segmented into gray matter, white matter, and CSF, and the warping fields obtained with cortical pattern matching is applied to the GM images, thus allowing measurement of GM at thousands of homologous cortical locations. The mean gray matter proportion is computed for each group, and statistical significance maps showing correlation between gray matter density and group (EOAD vs LOAD in apoE4 carriers, EOAD vs LOAD in noncarriers, carriers vs non-carriers) will be computed.The hippocampal formation will be isolated by manually tracing on 35 coronal slices the outlines of the hippocampus proper and subiculum after registration of original MRI to stereotactic space; a medial curve will be automatically defined as the 3D curve traced out by the centroid of the hippocampal boundary in each image slice. The radial size of each hippocampus at each boundary point will be assessed by automatically measuring the radial 3D distance from the surface points to the medial curve defined for individuals hippocampal surface model. Shorter radial distances will be used as an index of atrophy; statistical maps will be generated indicating local group differences in radial hippocampal distance.Expected results. ApoE could be associated with greater cortical atrophy in EOAD patients, and with greater hippocampal atrophy in LOAD.
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