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The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer's disease
| Content Provider | Scilit |
|---|---|
| Author | Badea, Alexandra Kane, Lauren Anderson, Robert J. Qi, Yi Foster, Mark Cofer, Gary P. Medvitz, Neil Buckley, Anne F. Badea, Andreas K. Wetsel, William C. Colton, Carol A. |
| Copyright Year | 2016 |
| Description | Journal: Neuroimage Multivariate biomarkers are needed for detecting Alzheimer's disease (AD), understanding its etiology, and quantifying the effect of therapies. Mouse models provide opportunities to study characteristics of AD in well-controlled environments that can help facilitate development of early interventions. The CVN-AD mouse model replicates multiple AD hallmark pathologies, and we identified multivariate biomarkers characterizing a brain circuit disruption predictive of cognitive decline. In vivo and ex vivo magnetic resonance imaging (MRI) revealed that CVN-AD mice replicate the hippocampal atrophy (6%), characteristic of humans with AD, and also present changes in subcortical areas. The largest effect was in the fornix (23% smaller), which connects the septum, hippocampus, and hypothalamus. In characterizing the fornix with diffusion tensor imaging, fractional anisotropy was most sensitive (20% reduction), followed by radial (15%) and axial diffusivity (2%), in detecting pathological changes. These findings were strengthened by optical microscopy and ultrastructural analyses. Ultrastructual analysis provided estimates of axonal density, diameters, and myelination—through the g-ratio, defined as the ratio between the axonal diameter, and the diameter of the axon plus the myelin sheath. The fornix had reduced axonal density (47% fewer), axonal degeneration (13% larger axons), and abnormal myelination (1.5% smaller g-ratios). CD68 staining showed that white matter pathology could be secondary to neuronal degeneration, or due to direct microglial attack. In conclusion, these findings strengthen the hypothesis that the fornix plays a role in AD, and can be used as a disease biomarker and as a target for therapy. |
| Related Links | http://europepmc.org/articles/pmc5159324?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159324/pdf |
| Ending Page | 511 |
| Page Count | 14 |
| Starting Page | 498 |
| ISSN | 10538119 |
| DOI | 10.1016/j.neuroimage.2016.08.014 |
| Journal | Neuroimage |
| Volume Number | 142 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2016-08-10 |
| Access Restriction | Open |
| Subject Keyword | Journal: Neuroimage Alzheimer's Disease Diffusion Tensor Imaging Electron Microscopy |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology Cognitive Neuroscience |
