High-resolution mapping of brain vasculature and its impairment in the hippocampus of Alzheimer's disease mice

• 来源期刊: 国家科学评论（英文版）
• 关键词: Micro-Optical Sectioning Tomography image optimization Alzheimer's disease impaired hippocampal vasculature virtual vascular endoscopy
• 年，卷（期）: 2019,（6）
• 页码范围: 1223-1238
• 页数: 16页
• 语种: 英文
• DOI: 10.1093/nsr/nwz124

摘要

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 gyrus (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 hippocampus 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 microcirculation for understanding AD pathogenesis.