Quantitative Assessment of Age-Associated Alterations in Brain Vasculature in Wild-Type Mice and in Bigenic Mice that Model Alzheimer's Disease.

Purpose: 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.

Procedures: 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.

Results: 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.

Conclusions: 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.