Dynamic changes in vascular size and density in transgenic mice with Alzheimer’s disease

Abstract

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.

Mapping of microvascular architecture in the brain of an Alzheimer's disease mouse model using MRI

“…A recent MRI-based study showed that the microvessel density in AD-model mice decreased, but mVD and VSI in AD-model mice increased in the regions of the hippocampus and brain cortex. 38 These were consistent with our results, which showed decreased Q and increased mVD and VSI in the cortex and hippocampus of AD-model mice. In addition, our results also showed changes in the dentate gyri and CA1 areas.…”

“…Another biochemistry study showed microvessel injury in the AD human brain caused by an accumulation of Aβ proteins. 37 This injury can be altered in mVD and VSI in our study and the previous one by Xu et al 38 We used MvWI (ΔR2* × ΔR2) as a voxel tool to map small blood vessels. This improves the sensitivity for visualizing intracortical penetrating arterioles and venules deep within the animal brain through segmentation and quantification.…”

“…Although a recent study showed increased mVD and VSI in AD-model mice, the authors did not provide results of the statistical analysis. 38 A previous immunohistochemistry study showed a decreased microvessel density during the late stage of AD-model mice. 29 However, our study and the previous one by Xu et al 38 did not show a significantly decreased microvascular density in all ROIs.…”

“…38 A previous immunohistochemistry study showed a decreased microvessel density during the late stage of AD-model mice. 29 However, our study and the previous one by Xu et al 38 did not show a significantly decreased microvascular density in all ROIs. Another biochemistry study showed microvessel injury in the AD human brain caused by an accumulation of Aβ proteins.…”

Cerebral Amyloid Angiopathy in a Mouse Model of Alzheimer’s Disease Associates with Upregulated Angiopoietin and Downregulated Hypoxia-Inducible Factor

“…Previous studies on postmortem human brains and AD mice models reported reductions in vascular density in cortex, hippocampus, and basal forebrain [6,10,44,45], but there is also considerable evidence of increased angiogenesis in both human and AD mice model brains [46][47][48][49]. Further, a recent study by Xu et al demonstrates a decrease in vascular density in aged APP23 mice, with a transient increase in density at 9 months [50]. It is worth noting that some studies and particularly older ones fail to take possible cortical atrophy into account (reviewed in [13]).…”