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Neurobiol Dis. 2013 Jun;54:59-67. doi: 10.1016/j.nbd.2013.02.005. Epub 2013 Feb 27.

Early cortical thickness changes predict β-amyloid deposition in a mouse model of Alzheimer's disease.

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  • 1Small Animal Imaging Lab, McConnell Brain Imaging Centre, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada. marilyn.grandmaison@mail.mcgill.ca

Abstract

Magnetic resonance imaging (MRI) studies have identified aberrant cortical structure in Alzheimer's disease (AD). The association between MRI-derived cortical morphometry measures and β-amyloid, however, remains poorly understood. In this study, we explored the potential relationship between early alterations in cortical thickness and later stage β-amyloid deposition, using a novel approach, in a transgenic AD mouse model. We acquired longitudinal anatomical MRI scans from mutant amyloid precursor protein (APP) transgenic mice and age-matched wild-type mice at 1 and 3.5months-of-age, and employed fully-automated image processing methods to derive objective, quantitative measures of cortical thickness on a region-of-interest basis. We also generated 3D quantitative immunohistochemistry (qIHC) volumes of deposited β-amyloid burden from 18month-old transgenic mice using an automated, production-level process. These studies revealed thinner cortex in most regions in the 1month-old transgenic mice relative to age-matched wild-types, with the exception of the frontal, perirhinal/entorhinal, posterior cingulate, and retrosplenial cortical regions. Between 1 and 3.5months-of-age, the transgenic mice demonstrated stable or increasing cortical thickness, while the wild-type mice showed cortical thinning. Based on data from co-registered 3D MRI and qIHC volumes, we identified an association between abnormal, early, regional cortical thickness change over 2.5months and later β-amyloid deposition. These observations suggest that the spatio-temporal pattern of early (pre-plaque) alterations in cerebral cortical structure is indicative of regional predisposition to later β-amyloid pathology in a transgenic AD mouse model.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMID:
23454197
[PubMed - indexed for MEDLINE]
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