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Anatomically-distinctgeneticassociations of APOE ɛ4 alleleload with regionalcorticalatrophy in Alzheimer's disease

Filippini, Nicola, Rao, Anil, Wetten, Sally, Gibson, Rachel A., Borrie, Michael, Guzman, Danilo, Kertesz, Andrew, Loy-English, Inge, Williams, Julie, Nichols, Thomas, Whitcher, Brandon and Matthews, Paul M. 2009. Anatomically-distinctgeneticassociations of APOE ɛ4 alleleload with regionalcorticalatrophy in Alzheimer's disease. NeuroImage 44 (3) , pp. 724-728. 10.1016/j.neuroimage.2008.10.003

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Abstract

APOEɛ4 is the best-established genetic risk factor for sporadic Alzheimer'sdisease (AD). However, while homozygotes show greater disease susceptibility and earlier age of onset than heterozygotes, they may not show faster rates of clinical progression. We hypothesize that there are differential APOEɛ4allele-load dependent influences on neuropathology across the brain. Our aim was to define the relationship between APOEɛ4alleleload and regionally-specific brain corticalatrophy in Alzheimer'sDisease (AD). For this reason voxel-based morphometry (VBM) was performed using T1-weighted MR images from 83 AD patients, contrasting regionalcortical grey matter by APOEɛ4load according to either dominant or genotypic models. Patients fulfilled NINCDS-ADRDA criteria and were genotyped for APOEɛ4 (15 ɛ4/ɛ4, 39 ɛ4/− and 29−/−). We observed that grey matter volume (GMV) decreased additively with increasing alleleload in the medial (MTL) and anterior temporal lobes bilaterally. By contrast, a 2 degree-of-freedom genotypic model suggested a dominant effect of the APOEɛ4allele in the left temporal lobe. Brain regions showing a significant APOEɛ4alleleload effect on GMV in AD included only some of those typically described as having greatest amyloid plaque deposition and atrophy. Temporal regions appeared to show a dominant effect of APOEɛ4alleleload instead of the additive effect previously strongly associated with age of onset. Regional variations with alleleload may be related to different mechanisms for effects of APOEɛ4load on susceptibility and disease progression.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Elsevier
ISSN: 1053-8119
Last Modified: 04 Jun 2017 03:45
URI: http://orca.cf.ac.uk/id/eprint/26105

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