| First Author | Grand'maison M | Year | 2013 |
| Journal | Neurobiol Dis | Volume | 54 |
| Pages | 59-67 | PubMed ID | 23454197 |
| Mgi Jnum | J:197951 | Mgi Id | MGI:5494932 |
| Doi | 10.1016/j.nbd.2013.02.005 | Citation | Grand'maison M, et al. (2013) Early cortical thickness changes predict beta-amyloid deposition in a mouse model of Alzheimer's disease. Neurobiol Dis 54:59-67 |
| abstractText | Magnetic resonance imaging (MRI) studies have identified aberrant cortical structure in Alzheimer's disease (AD). The association between MRI-derived cortical morphometry measures and beta-amyloid, however, remains poorly understood. In this study, we explored the potential relationship between early alterations in cortical thickness and later stage beta-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 beta-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 beta-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 beta-amyloid pathology in a transgenic AD mouse model. |
