Ventura-Antunes Lissa, Nackenoff Alex, Romero-Fernandez Wilber, Wang Yongchao, Bosworth Allison M, Prusky Alex, Wang Emmeline, Carvajal-Tapia Cristian, Shostak Alena, Harmsen Hannah, Mobley Bret, Maldonado Jose, Womble Neely, Solopova Elena, Snider J Caleb, Merryman W David, Lippmann Ethan S, Schrag Matthew
Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Alzheimers Dement. 2025 Jun;21(6):e70254. doi: 10.1002/alz.70254.
The morphological and molecular changes associated with the degeneration of arterioles in cerebral amyloid angiopathy (CAA) are incompletely understood.
Post mortem brains from 26 patients with CAA or neurological controls were analyzed using light-sheet microscopy, and morphological features of microvascular degeneration were quantified using surface volume rendering. Vascular stiffness was analyzed using atomic force microscopy.
Vascular smooth muscle cells (VSMCs) volume was reduced by ≈ 55% in CAA. This loss of VSMC volume correlated with increased arteriolar diameter, variability in diameter, and the volume of amyloid beta (Aβ) deposition in the vessel. Vessels with CAA were > 300% stiffer than controls. The volume of extracellular matrix cross-linking enzyme lysyl oxidase (LOX) correlated closely with vascular degenerative features.
Our findings provide valuable insights into the connections among LOX, Aβ deposition, and vascular stiffness in CAA. Restoration of physiologic extracellular matrix properties in penetrating arteries may yield a novel therapeutic strategy for CAA.
We conducted 3D microscopy on human brains with cerebral amyloid angiopathy. We quantified features of vascular degeneration, β-amyloid, and lysyl oxidase in CAA Vascular degeneration correlated with Aβ, loss of VSMCs , and increased LOX. Arterioles with CAA were stiffer than controls in data from atomic force microscopy. Vascular extracellular matrix properties may be a therapeutic target for CAA.
与脑淀粉样血管病（CAA）中小动脉退变相关的形态学和分子变化尚未完全明确。
使用光片显微镜对26例CAA患者或神经学对照的尸检大脑进行分析，采用表面容积渲染对微血管退变的形态学特征进行量化。使用原子力显微镜分析血管硬度。
CAA中血管平滑肌细胞（VSMC）体积减少约55%。VSMC体积的减少与小动脉直径增加、直径变异性以及血管中淀粉样β蛋白（Aβ）沉积量相关。患有CAA的血管比对照血管硬300%以上。细胞外基质交联酶赖氨酰氧化酶（LOX）的体积与血管退变特征密切相关。
我们的研究结果为CAA中LOX、Aβ沉积和血管硬度之间的联系提供了有价值的见解。恢复穿通动脉中生理细胞外基质特性可能为CAA带来一种新的治疗策略。
我们对患有脑淀粉样血管病的人类大脑进行了三维显微镜检查。我们量化了CAA中血管退变、β淀粉样蛋白和赖氨酰氧化酶的特征。血管退变与Aβ、VSMC丢失和LOX增加相关。在原子力显微镜数据中，患有CAA的小动脉比对照更硬。血管细胞外基质特性可能是CAA的治疗靶点。
