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<i>In Vivo</i> Longitudinal Monitoring of Changes in the Corpus Callosum Integrity During Disease Progression in a Mouse Model of Alzheimer’s Disease

[ Vol. 12 , Issue. 10 ]

Author(s):

F. Kara, C. Höfling, S. Roßner, R. Schliebs, A. Van der Linden, H.J.M. Groot and A. Alia   Pages 941 - 950 ( 10 )

Abstract:


The corpus callosum is the largest commissural fiber connecting left and right hemisphere of the brain. Emerging evidence suggests that a variety of abnormalities detected in the microstructure of this white matter fiber can be an early event in Alzheimer&#039;s disease (AD) pathology. However, little is known about tissue characteristics of these abnormalities and how these abnormalities evolve during AD progression. In this study, we measured in vivo magnetic resonance transverse relaxation times (T<sub>2</sub>) to longitudinally monitor changes in tissue integrity and abnormalities related to myelination and demyelination processes in corpus callosum of AD mouse models. The most striking finding of our study was a significant elongation of T<sub>2</sub> values in the corpus callosum at 10, 14, 16 and 18 months of age compared to age-matched wild-type mice. In contrast, the gray matter regions surrounding the corpus callosum, such as the cortex and hippocampus, showed a significant T<sub>2</sub> decrease compared to wild-type mice. Histological analyses clearly revealed demyelination, gliosis and amyloid-plaque deposition in the corpus callosum. Our results suggest that demyelinating and inflammatory pathology may result in prolonged relaxation time during AD progression. To our knowledge, this is the first in vivo T<sub>2</sub> study assessing the microstructural changes with age in the corpus callosum of the Tg2576 mouse model and it demonstrates the application of T<sub>2</sub> measurement to noninvasively detect tissue integrity of the corpus callosum, which can be an early event in disease progression.

Keywords:

Alzheimer’s disease, T<sub>2</sub> relaxation time, corpus callosum, demyelination, gliosis, longitudinal study, Tg2576 mouse model.

Affiliation:

, , , , , , Leiden Institute of Chemistry, Gorlaeus Laboratoria, Einsteinweg 55, P.O. Box 9502, 2300 RA Leiden, The Netherlands; Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, D-04109 Leipzig, Germany; Institute of Medical Physics and Biophysics, University of Leipzig, D-04107 Leipzig, Germany.



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