Cited by 39Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeurological Disease Mechanisms and Treatments

The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer’s disease.

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Badea, Alexandra, Kane, Lauren, Anderson, Robert J., Qi, Yi, Foster, Mark, Cofer, Gary P., Medvitz, Neil, Buckley, Anne F. +3 more·2016·NeuroImage

Abstract

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.

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Research works printed but not linked: 3

  1. Fox JGA The Mouse in Biomedical Research [electronic resource]: History, Wild Mice, and Genetics. Elsevier Jan 2007 Ipswich 2007 New York Ebsco Publishing [Distributor]
  2. Jack CR Jr Petersen RC Xu YC O’Brien PC Smith GE Ivnik RJ Boeve BF Waring SC Tangalos EG Kokmen E Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment Neurology 1999 52 1397 1403 10227624 PMC2730146
  3. Jack CR Jr Petersen RC Xu YC Waring SC O’Brien PC Tangalos EG Smith GE Ivnik RJ Kokmen E Medial temporal atrophy on MRI in normal aging and very mild Alzheimer’s disease Neurology 1997 49 786 794 9305341 PMC2730601

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Authors
Badea, A., Kane, L., Anderson, R. J., Qi, Y., Foster, M., Cofer, G. P., Medvitz, N., Buckley, A. F., Badea, A. K., Wetsel, W. C., & Colton, C. A.
Affiliations
  • Duke University (US)
  • Duke Medical Center (US)
Corresponding author
Badea, Alexandra
Venue
NeuroImage
Publisher
Elsevier BV
Published
2016-11
Volume
142
Pages
498-511
ISSN
1053-8119 (ISSN-L)
OpenAlex
W2507413010
Cited by
39
References
109
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 1
FWCI
3.49
Type
journal article
Language
en
Open access
Locations
  • NeuroImage (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (P41 EB015897, 1S10OD010683-01, R01 AG045422, K01 AG041211)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
Alzheimer's disease, fornix, hippocampal atrophy, white matter pathology, fractional anisotropy, g-ratio, axonal degeneration, myelination, microglial activation, cognitive decline, diffusion tensor imaging
MeSH terms
Alzheimer Disease, Animals, Atrophy, Disease Models, Animal, Hippocampus, Mice, Transgenic, Microscopy, Electron, Biomarkers, Fornix, Brain, Mice, Diffusion Tensor Imaging, White Matter

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