Abstract

ApoliopoproteinE ε4 (ApoE-ε4) polymorphism is the most well known genetic risk factor for developing Alzheimers Disease. The exact mechanism through which ApoE ε4 increases AD risk is not fully known, but may be related to decreased clearance and increased oligomerization of Aβ. By making measurements of white matter integrity via diffusion MR and correlating the metrics in a voxel-based statistical analysis with ApoE-ε4 genotype (whilst controlling for vascular risk factor, gender, cognitive status and age) we are able to identify changes in white matter associated with carrying an ApoE ε4 allele. We found potentially significant regions (Puncorrected < 0.05) near the hippocampus and the posterior cingulum that were independent of voxels that correlated with age or clinical dementia rating (CDR) status suggesting that ApoE may affect cognitive decline via a pathway in dependent of normal aging and acute insults that can be measured by CDR and Framingham Coronary Risk Score (FCRS).

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