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

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 )  × 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 P P  = 0.0311). Normalising regional volumes to whole brain measurements revealed significant, prolonged, WT-TASTPM volume differences, suggesting transgene effects establish at