In vivo MRI and histological evaluation of brain atrophy in APP/PS1 transgenic mice

Regional cerebral atrophy was evaluated in APP/PS1 mice harboring mutated transgenes linked to familial Alzheimer's disease, using complementary methods. In vivo high resolution MRI was selected for measurements of brain atrophy and associated cerebrospinal fluid dilation; histological analysis was performed to reveal localized atrophies and to evaluate amyloid burden. Young APP/PS1 mice examined at a pre-amyloid stage (10 weeks) showed disruption in development (reduced intracranial and brain volumes). Comparison of young and old (24 months) mice, indicated that both APP/PS1 and control brains endure growth during adulthood. Aged APP/PS1 animals showed a moderate although significant global brain atrophy and a dilation of CSF space in posterior brain regions. The locus of this atrophy was identified in the midbrain area and not, as expected, at isocortical/hippocampal levels. Atrophy was also detected in fiber tracts. The severity of brain atrophy in old APP/PS1 mice was not correlated with the extent of cerebral amyloidosis. The relevance of current transgenic mouse models for the study of brain atrophy related to Alzheimer's disease is discussed. (c) 2005 Elsevier Inc. All rights reserved.