Association of vascular amyloid beta and cells of the mononuclear phagocyte system in hereditary cerebral hemorrhage with amyloidosis (Dutch) and Alzheimer disease
Association of vascular amyloid beta and cells of the mononuclear phagocyte system in hereditary cerebral hemorrhage with amyloidosis (Dutch) and Alzheimer disease
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DOI：
10.1097/00005072-199703000-00006
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发表时间：
1997-03-01
影响因子：
3.2
通讯作者：
Roos, RAC
中科院分区：
文献类型：
--
作者：
MaatSchieman, MLC;vanDuinen, SG;Roos, RAC
应用Aβ、α-平滑肌肌动蛋白和单核/巨噬细胞标志物(HLA-DR、CD68、CD11c、CD45)免疫组织化学方法，研究了遗传性脑出血伴淀粉样变性(HCHWA-D)和阿尔茨海默病(AD)脑淀粉样血管病(CAA)患者动脉和小动脉淀粉样β蛋白(Aβ)沉积的形态、范围及其与单核巨噬细胞系统(MPS)细胞的关系。HCHWA-D/AD动脉/小动脉中膜表现为致密的Aβ沉积，首先出现在中膜/外膜交界处，并伴有平滑肌丢失。只有HCHWA-D CAA的特点是：(A)较大的动脉严重受累，(B)小动脉显示单环或双环的放射状Aβ环绕致密的Aβ。放射状Aβ似乎在中膜/外膜交界处发育。单核/巨噬细胞标记阳性的病灶/细胞与HCHWA-D动脉Aβ共定位。在AD/HCHWA-D动脉的中膜/外膜交界处，在缺乏局部Aβ的情况下，可观察到局部的HLA-DR/CD11c阳性，而对照组则未见。与放射状Aβ共定位的单核/巨噬细胞标记阳性呈连续性，血管周围细胞和小胶质细胞聚集在血管周围。这些结果提示：(A)MPS细胞与HCHWA-D动脉Aβ和放射状小动脉Aβ存在局部联系；(B)在Aβ之前，HLADR/CD11c免疫反应可能出现在中膜/外膜交界处。后者的发现和假定的中膜/外膜交界处放射状Aβ的形成可能与腔基底膜参与CAA的发病有关。MPS细胞在这一过程中的作用仍有待确定。
Arterial and arteriolar amyloid-beta (A beta) deposition in hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) and Alzheimer disease (AD) cerebral amyloid angiopathy (CAA) were studied as to morphology, extent, and association with mononuclear phagocyte system (MPS) cells using A beta, a-smooth muscle actin, and monocyte/macrophage marker (HLA-DR, CD68, CD11c, CD45) immunohistochemistry. The HCHWA-D/AD arterial/arteriolar media showed compact A beta deposits, first appearing at the media/adventitia junction, and concomitant smooth muscle loss. Only HCHWA-D CAA featured (a) severe involvement of larger arteries and (b) arterioles showing a single or double ring of radial A beta surrounding compact A beta. Radial A beta appeared to develop at the media/adventitia junction. Monocyte/macrophage marker-positive foci/cells co-localized with HCHWA-D arterial A beta. Focal HLA-DR/CD11c positivity was observed at the media/adventitia junction of AD/HCHWA-D arteries in the absence of local A beta, but not in controls. Monocyte/macrophage marker positivity co-localizing with radial A beta appeared continuous with perivascular cells and microglia clustering perivascularly. These results suggest that (a) MPS cells are topographically associated with HCHWA-D arterial A beta and radial arteriolar A beta, and (b) HLA-DR/CD11c immunoreactivity may appear at the media/adventitia junction prior to A beta. The latter finding and the assumed formation of radial A beta at the media/adventitia junction may relate to involvement of the abluminal basement membrane in CAA pathogenesis. The role of MPS cells in this process remains to be established.