Classic β-amyloid deposits cluster around large diameter blood vessels rather than capillaries in sporadic Alzheimer's disease
Classic β-amyloid deposits cluster around large diameter blood vessels rather than capillaries in sporadic Alzheimer's disease
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DOI：
10.2174/156720206778792948
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发表时间：
2006-11-01
影响因子：
2.1
通讯作者：
Armstrong, Richard A.
中科院分区：
文献类型：
--
作者：
Armstrong, Richard A.
不同的假说可以解释阿尔茨海默病(AD)中β-淀粉样蛋白(AP)沉积与血管系统的关系。淀粉样蛋白沉积可降低毛细血管密度，影响血管内皮细胞，导致血管扩散，或干扰血管周围清除机制。因此，我们研究了9例散发性阿尔茨海默病(SAD)患者额上回上叶Aβ沉积的典型(“核心”)型的空间分布模式。切片：AP抗体免疫组织化学染色和IV型胶原免疫组织化学染色，研究经典沉积的空间分布与血管形态的关系。经典的沉积物和血管轮廓都是成簇分布的。在所有病例中，典型沉积的聚集性与较大直径(-gt；10微米)的血管轮廓，尤其是垂直穿透小动脉之间存在正相关。仅在一种情况下，经典沉积的集群与较小直径(<；10微米)的毛细血管之间存在显著的空间相关性。AP沉积密度与毛细血管直径较小无显著负相关。在9/11例中，典型沉积的斑块明显大于较大血管轮廓的斑块。此外，典型沉积物的密度下降--与垂直穿透小动脉的距离呈负指数函数关系。这些结果表明，经典的AP沉积聚集在额叶皮质上层较大的血管周围。这种聚集可能是由于蛋白质从血管扩散，或者是由于血管周围清除系统从大脑超载造成的。
Various hypotheses could explain the relationship between beta-amyloid (AP) deposition and the vasculature in Alzheimer's disease (AD). Amyloid deposition may reduce capillary density, affect endothelial cells of blood vessels, result in diffusion from blood vessels, or interfere with the perivascular clearance mechanism. Hence, the spatial pattern of the classic ('cored') type of A beta deposit was studied in the upper laminae of the superior frontal gyrus in nine cases of sporadic AD (SAD). Sections were : immunostained with antibodies against AP and with collagen IV to study the relationships between the spatial distribution of the classic deposits and the blood vessel profiles. Both the classic deposits and blood vessel profiles -were distributed in clusters. In all cases, there was a positive spatial correlation between the clusters of the classic deposits and the larger diameter (> 10 mu m) blood vessel profiles and especially the vertically penetrating arterioles. In only I case, was there a significant spatial correlation between the clusters of the classic deposits and the smaller diameter (< 10 mu m) capillaries. There were no negative correlations between the density of Ap deposits and the smaller diameter capillaries. In 9/11 cases, the clusters of the classic deposits were significantly larger than those of the clusters of the larger blood vessel profiles. In addi.tion, the density of the classic deposits declined -as a negative exponential function with distance from a vertically penetrating arteriole. These results suggest that the classic AP deposits cluster around the larger blood vessels in the upper laminae of the frontal cortex. This aggregation could result from diffusion of proteins from blood vessels or from overloading the system of perivascular clearance from the brain.