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Longitudinal regional brain volume changes quantified in normal aging and Alzheimer's APP x PS1 mice using MRI

Item Type:Article
Title:Longitudinal regional brain volume changes quantified in normal aging and Alzheimer's APP x PS1 mice using MRI
Creators Name:Maheswaran, S. and Barjat, H. and Rueckert, D. and Bate, S.T. and Howlett, D.R. and Tilling, L. and Smart, S.C. and Pohlmann, A. and Richardson, J.C. and Hartkens, T. and Hill, D.L.G. and Upton, N. and Hajnal, J.V. and James, M.F.
Abstract:In humans, mutations of amyloid precursor protein (APP) and presenilins (PS) 1 and 2 are associated with amyloid deposition, brain structural change and cognitive decline, like in Alzheimer's disease (AD). Mice expressing these proteins have illuminated neurodegenerative disease processes but, unlike in humans, quantitative imaging has been little used to systematically determine their effects, or those of normal aging, on brain structure in vivo. Accordingly, we investigated wildtype (WT) and TASTPM mice (expressing human APP(695(K595N, M596L)) x PS1(M146V)) longitudinally using MRI. Automated global and local image registration, allied to a standard digital atlas, provided pairwise segmentation of 13 brain regions. We found the mature mouse brain, unlike in humans, enlarges significantly from 6-14 months old (WT 3.8+/-1.7%, mean+/-SD, P<0.0001). Significant changes were also seen in other WT brain regions, providing an anatomical benchmark for comparing other mouse strains and models of brain disorder. In TASTPM, progressive amyloidosis and astrogliosis, detected immunohistochemically, reflected even larger whole brain changes (5.1+/-1.4%, P<0.0001, transgenexage interaction P=0.0311). Normalising regional volumes to whole brain measurements revealed significant, prolonged, WT-TASTPM volume differences, suggesting transgene effects establish at <6 months old of age in most regions. As in humans, gray matter-rich regions decline with age (e.g. thalamus, cerebral cortex and caudoputamen); ventricles and white matter (corpus callosum, corticospinal tract, fornix system) increase; in TASTPMs such trends often varied significantly from WT (especially hippocampus). The pervasive, age-related structural changes between WT and AD transgenic mice (and mouse and human) suggest subtle but fundamental species differences and AD transgene effects.
Keywords:Aging, Alzheimer's Disease, Structural MRI, Transgenic, APP/PS1, TASTPM, Animals, Mice
Source:Brain Research
ISSN:0006-8993
Publisher:Elsevier (The Netherlands)
Volume:1270
Page Range:19-32
Date:13 May 2009
Official Publication:https://doi.org/10.1016/j.brainres.2009.02.045
PubMed:View item in PubMed

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