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IC‐P1‐019: Patterns of cerebral atrophy and neuropathological alterations in mouse lemur primates suggest an evolutive disease
Author(s) -
Dhenain Marc,
Mestre-Frances Nadine,
Dorieux Olene,
Petit Fanny,
Picq Jean-Luc,
Herard Anne-Sophie,
Chenu Evelyne,
Volk Andreas,
Perret Martine,
Hantraye Philippe,
Aujard Fabienne
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.030
Subject(s) - atrophy , pathology , cerebral atrophy , cerebral cortex , biology , voxel , anatomy , medicine , neuroscience , radiology
Background: Cerebral atrophy is a common pattern in Alzheimer’s disease and in many other neurodegenerative processes (1). It is also reported in aged mouse lemur primates (2). These small animals (12 cm, maximal life span of 12 years) can also display diffuse amyloid depositions and tau pathology while aging (3). Methods: The location of cerebral atrophy was assessed in 31 mouse lemurs aged from 1.9 to 11.3 years. 3D MR images (isotropic resolution 234 m) were recorded on a 4.7T Bruker system. An automatic segmentation technique was used to detect cerebro-spinal fluid (CSF) voxels in areas surrounding the cortex (2). Then, CSF voxels surrounding various functional regions (frontal and parietal (FPcort), parieto-temporal (PTcort), temporal (Tcort), occipital (Ocort) cortices) were manually labeled and counted. Histological evaluation (amyloid (anti-A 4G8 antibodies (Biovalley, France)) and GFAP stainings) was also performed in 7 lemurs (6.4 to 11.2 years) previously evaluated by MRI. Results: Significant CSF increase in pericortical regions was detected in only one young animal. The prevalence of cerebral atrophy increased with age (25% and 75% in middle aged and old animals), following a characteristic, sequential, pattern. First, some animals (n 3) displayed CSF accumulation in regions surrounding the FPcort (stage 1). In five animals, in addition to FPcort, the atrophy process involved one cortical region adjacent to FPcort. In 4 animals, this additional region was PTcort (stage 2a) while it was Tcort for one animal (stage 2b). In 2 additional animals, the atrophy process involved FPcort, PTcort and Tcort (stage 3). Finally, in 5 animals the atrophy involved FPcort, PTcort, Tcort, and Ocort. Only two of these lemurs had extracellular amyloid deposits. Most of these severely atrophied animals had intracellular amyloid deposits in cortical and hippocampal regions and activated glial accumulation. Conclusions: Our data suggest that cerebral atrophy in mouse lemurs follows a sequential pathway and that neuropathological alterations other than extracellular amyloid deposition should be investigated to explain the brain atrophy. Acknowledgements: Longevity-GIS, ‘NeuroscienceACI-programs’ (French Minister for Research), France-Alzheimer-Association.