Monitoring blood flow alterations in the Tg2576 mouse model of Alzheimer's disease by in vivo magnetic resonance angiography at 17.6 T

Many neurodegenerative diseases including Alzheimer's disease are linked to abnormalities in the vascular system. In AD, the deposition of amyloid beta (A beta) peptide in the cerebral vessel walls, known as cerebral amyloid angiopathy (CAA) is frequently observed, leading to blood flow abnormalities. Visualization of the changes in vascular structure is important for early diagnosis and treatment. Blood vessels can be imaged non-invasively by magnetic resonance angiography (MRA). In this study we optimized high resolution MRA at 17.6 T to longitudinally monitor morphological changes in cerebral arteries in a Tg2576 mouse model, a widely used model of AD. Our results at 17.6 T show that MRA significantly benefits from the ultra-high magnetic field strength especially to visualize smaller vessels. Visual and quantitative analysis of MRA results revealed severe blood flow defects in large and medium sized arteries in Tg2576 mice. In particular blood flow defects were observed in the middle cerebral artery (MCA) and in the anterior communicating artery (AComA) in Tg2576 mice. Histological data show that A beta levels in the vessel wall may be responsible for impaired cerebral blood flow, thereby contributing to the early progression of AD. To our knowledge this is the first ultra-high field MRA study monitoring blood flow alterations longitudinally in living Tg2576 mice, consequently providing a powerful tool to test new therapeutic intervention related to CAA in a mouse model of AD. (c) 2011 Elsevier Inc. All rights reserved.