期刊
NATIONAL SCIENCE REVIEW
卷 6, 期 6, 页码 1223-1238出版社
OXFORD UNIV PRESS
DOI: 10.1093/nsr/nwz124
关键词
Micro-Optical Sectioning Tomography; image optimization; Alzheimer's disease; impaired hippocampal vasculature; virtual vascular endoscopy
资金
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX05]
- National Science Fund for Distinguished Young Scholars [81825021]
- Youth Innovation Promotion Association CAS [2018323]
Accumulating evidence indicates the critical importance of cerebrovascular dysfunction in the pathogenesis of Alzheimer's disease (AD). However, systematic comparative studies on the precise brain vasculature of wild-type and AD model mice are still rare. Using an image-optimization method for analysing Micro-Optical Sectioning Tomography (MOST) data, we generated cross-scale whole-brain 3D atlases that cover the entire vascular system from large vessels down to smallest capillaries at submicron resolution, for both wild-type mice and a transgenic (APP/PS1) mouse model of AD. In addition to distinct vascular patterns in different brain regions, we found that the main vessels of the molecular layer of the hippocampal dentate gyms (DG-ml) undergo abrupt changes in both diameter and branch angle, spreading a unique comb-like pattern of capillaries. By using a quantitative analysis workflow, we identified in the hippo campus of AD mice an overall reduction of the mean vascular diameter, volume fraction and branch angle, with most significant impairment in the DG-ml. In addition, virtual endoscopy revealed irregular morphological features in the vessel lumen of the AD mice, potentially contributing to the impairment of blood flow. Our results demonstrate the capability of high-resolution cross-scale evaluation of brain vasculature and underscore the importance of studying hippocampal micro circulation for understanding AD pathogenesis.
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