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Age-associated cerebral atrophy in mouse lemur primates
Authors:Audrey Kraska  Olene Dorieux  Jean-Luc Picq  Fanny Petit  Emmanuel Bourrin  Evelyne ChenuAndreas Volk  Martine PerretPhilippe Hantraye  Nadine Mestre-FrancesFabienne Aujard  Marc Dhenain
Affiliation:a CEA, DSV, I2BM, MIRCen, 18 route du panorama, 92265 Fontenay-aux-Roses Cedex, France
b CNRS, URA CEA CNRS 2210, 18 route du panorama, 92265 Fontenay-aux-Roses Cedex, France
c CNRS UMR 7179, MNHN, 4 Av du Petit Château, 91800 Brunoy, France
d Laboratoire de psychopathologie et de neuropsychologie, E.A. 2027, Université Paris 8, 2 rue de la liberté, 93000 St Denis, France
e Institut de Recherche SERVIER, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, France
f Institut Curie, U759 INSERM, Centre Universitaire, Labo 112, 91405 Orsay Cedex, France
g INSERM U710, EPHE, Université Montpellier 2, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France
h CEA, DSV, I2BM, NeuroSpin, Centre CEA de Saclay, Bât. 145, 91191 Gif sur Yvette, France
Abstract:We assessed the regional brain atrophy in mouse lemur primates from 4.7 T T2-weighted magnetic resonance images. Thirty animals aged from 1.9 to 11.3 years were imaged. Sixty-one percent of the 23 animals older than 3 years involved in the study displayed an atrophy process. Cross-sectional analysis suggests that the atrophy follows a gradual pathway, starting in the frontal region then involving the temporal and/or the parietal part of the brain and finally the occipital region. Histological evaluation of five animals selected according to various stages of atrophy suggested that extracellular amyloid deposits and tau pathology cannot explain by themselves this atrophy and that intracellular amyloid deposition is more closely linked to this pathology. This study suggests that most of the age-related atrophy occurring in mouse lemurs is caused by one clinical, evolving, pathological process. The ability to follow this pathology non-invasively by MRI will allow to further characterize it and evaluate its relationship with neuropathological lesions that are involved in human diseases such as Alzheimer.
Keywords:Alzheimer's disease   Amyloid   Animal models   Atrophy   MRI   Tau
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