Quantitative Assessment of Age-Associated Alterations in Brain Vasculature in Wild-Type Mice and in Bigenic Mice that Model Alzheimer’s Disease
Vascular dysfunction is a major hallmark of Alzheimer’s disease (AD). However, studies that investigated vascular dysfunction in mice modeling AD using magnetic resonance angiography (MRA) are typically limited to qualitative and/or scoring-based paradigms, which are labor-intensive and observer-dependent.
We developed and validated a semi-automatic MRA processing pipeline and applied this to high-resolution in vivo MRA images acquired on a 9.4T small animal MRI scanner. We assessed vascular morphology at 3, 6, and 12 months in wild-type (WT) and bigenic (APP.V717IxTau.P301L: biAT) mice.
Vessel radius or length can increase with age regardless of genotype depending on the respective vessel. We also observed significantly lower internal carotid artery length in biAT mice compared to WT.
The results demonstrate that even subtle changes in vessel morphology can be noninvasively quantified. This is of great interest for AD, but also to other models of neurodegenerative diseases involving macrovascular dysfunction.
Key wordsAlzheimer’s disease Magnetic resonance angiography Neurovasculature Segmentation Morphometry Aging
The European Commission supported the INMiND project (FP7, Health-F2-2011-278850) and the PANA project (H2020-NMP-12-2015-686009). The Flemish government (Innovation through Science and Technology) supported the IWT MIRIAD (SBO 130065) project. The Research Foundation Flanders supported KG (FWO scholarship 11N0714N) and TD (FWO-KaN 184.108.40.206N). University of Leuven supported the Program Financing IMIR (10/017).
Compliance with Ethical Standards
Experiments were performed in accordance with regional, national, and international standards on animal welfare, in particular European Union Directive 2010/63/EU, and approved and overseen by the Animal Care and Ethical Committees of the University of Leuven.
Conflict of Interest
The authors declare that they have no conflicts of interest.
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