Research Paper Volume 12, Issue 17 pp 17224—17234
Dynamic changes in vascular size and density in transgenic mice with Alzheimer’s disease
- 1 Institute on Aging and Brain Disorders, First University Affiliated Hospital, Neurodegenerative Disorder Research Center, Division of Life and Medical Sciences, University of Science and Technology of China, Hefei Material Science National Laboratory at Microscale, CAS-Key Laboratory of Brain Functions and Brain Disorders, Center for Excellent in Brain Science and Intelligence Technology, Hefei, China
- 2 Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- 3 School of Medicine, Tongji University, Shanghai, China
- 4 Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, Zhejiang, China
- 5 High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, China
- 6 Key Laboratory of Anhui Province for High Field Magnetic Resonance Imaging, Hefei, China
- 7 Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
Received: November 28, 2019 Accepted: June 29, 2020 Published: September 9, 2020
https://doi.org/10.18632/aging.103672How to Cite
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.
Abbreviations
AD: Alzheimer’s disease; Aβ: Amyloid β; MRI: magnetic resonance imaging; mVD: the mean vessel diameter; VSI: the vessel size index; APP23: amyloid precursor protein 23; WT: wild-type; ROI: regions of interesting; TR: repetition time; TE: echo time; FOV: field of view; ADC: apparent diffusion coefficient; DWI: diffusion-weighted imaging; USPIO: ultra-small superparamagnetic iron oxide; T2WI: T2 weighted imaging; T2*WI: T2* weighted imaging; MATLAB: Matrix Laboratory; ET-1: endothelin-1; VEGF: vascular endothelial growth factor; bFGF: basic fibroblast growth factor; PDGF: platelet-derived growth factor.