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

Autor: Marilyn Grand'Maison, Simone P. Zehntner, Ming-Kai Ho, François Hébert, Andrew Wood, Felix Carbonell, Alex P. Zijdenbos, Edith Hamel, Barry J. Bedell
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Neurobiology of Disease, Vol 54, Iss , Pp 59-67 (2013)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2013.02.005
Popis: 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 3.5 months-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 18 month-old transgenic mice using an automated, production-level process. These studies revealed thinner cortex in most regions in the 1 month-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 3.5 months-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 2.5 months 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.
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