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

Title:In Vivo Longitudinal Monitoring of Changes in the Corpus Callosum Integrity During Disease Progression in a Mouse Model of Alzheimer’s Disease

Volume: 12 Issue: 10

Author(s): F. Kara, C. Höfling, S. Roßner, R. Schliebs, A. Van der Linden, H.J.M. Groot and A. Alia

Affiliation:

Keywords: Alzheimer’s disease, T₂ relaxation time, corpus callosum, demyelination, gliosis, longitudinal study, Tg2576 mouse model.

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'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 (T₂) 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 T₂ 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 T₂ 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 T₂ study assessing the microstructural changes with age in the corpus callosum of the Tg2576 mouse model and it demonstrates the application of T₂ measurement to noninvasively detect tissue integrity of the corpus callosum, which can be an early event in disease progression.

Cite this article as:

Kara F., Höfling C., Roßner S., Schliebs R., der Linden Van A., Groot H.J.M. and Alia A., In Vivo Longitudinal Monitoring of Changes in the Corpus Callosum Integrity During Disease Progression in a Mouse Model of Alzheimer’s Disease, Current Alzheimer Research 2015; 12 (10) . https://dx.doi.org/10.2174/1567205012666151027123728