In vivo MRI and histological evaluation of brain atrophy in APP/PS1 transgenic mice
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Benoît Delatour1, Maryvonne Guégan, Andreas Volk
1Laboratoire NAMC, CNRS, UMR 8620, Bât 446, Université Paris Sud, 91405 Orsay, France.
Abstract:
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.
Insights
Alzheimer
Area of Science:
- Neuroscience
- Biomedical Imaging
- Genetics
Background:
- Familial Alzheimer's disease (AD) is linked to specific genetic mutations.
- APP/PS1 transgenic mice are models for studying AD pathogenesis.
- Cerebral atrophy is a hallmark of neurodegenerative diseases like AD.
Purpose of the Study:
- To evaluate regional cerebral atrophy in APP/PS1 mice using MRI and histology.
- To investigate the relationship between brain atrophy and amyloid burden in AD models.
- To assess developmental and age-related brain volume changes in APP/PS1 mice.
Main Methods:
- In vivo high-resolution magnetic resonance imaging (MRI) for brain volume and cerebrospinal fluid (CSF) space.
- Histological analysis to determine localized atrophy and amyloid deposition.
- Comparative study of young (pre-amyloid) and aged (24 months) APP/PS1 and control mice.
Main Results:
- Young APP/PS1 mice showed developmental disruption with reduced brain volumes.
- Aged APP/PS1 mice exhibited moderate global brain atrophy and posterior CSF dilation.
- Atrophy was localized to the midbrain and fiber tracts, not typically affected cortical areas.
- Brain atrophy severity did not correlate with amyloid burden in aged mice.
Conclusions:
- APP/PS1 mouse models display distinct patterns of brain atrophy.
- Midbrain and fiber tracts are affected areas in this AD model.
- The lack of correlation between atrophy and amyloid suggests complex disease mechanisms.
