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

Abstract

Purpose: Vascular disfunction 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.

Neuroimaging of Mouse Models of Alzheimer’s Disease

“…In contrast, no autoregulatory changes in APP were reported in this single study [ 169 ]. MRI measures of vascular morphology in the APP.V717IxTau.P301L: biAT mice at 3, 6, and 12 months of age showed increasing vessel radius or length with age regardless of genotype, but the biAT mice had significantly lower internal carotid artery length, although the significance is not immediately clear [ 170 ]. Reductions in perfusion and blood volume were observed in the occipital cortex of B6.PS2APP mice [ 171 ].…”