Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Here, we used vessel size imaging to investigate the specific microvascular changes and most susceptible brain regions during AD progression in an amyloid precursor protein 23 (APP23) transgenic AD mouse model. Using 9.4 Tesla magnetic resonance imaging (MRI), the values of microvascular density (Density), mean vessel diameter (mVD), and vessel size index (VSI) were compared between APP23 and wild-type (WT) mice at 3, 6, 9, 14, and 20 months of age. Our results demonstrate that in 20-month old APP23 and WT mice, the Density values were significantly decreased, while the vascular dilatation and diameter had increased. However, a transient increase in the cortex Density at 14-months was observed in APP23 mice. Additionally, our results suggest that the hippocampus is the susceptible brain region affected by the abnormal microvascular angiogenesis during the early stages of AD. Together, our findings indicate that vessel size imaging using MRI can provide novel biomarkers for the early detection of AD, and for monitoring the effects of vascular-targeted therapeutics in AD.