Maat-Schieman M L, Rozemuller A J, van Duinen S G, Haan J, Eikelenboom P, Roos R A
Department of Neurology, University Hospital Leiden, The Netherlands.
J Neuropathol Exp Neurol. 1994 Sep;53(5):483-91. doi: 10.1097/00005072-199409000-00007.
In hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D) beta/A4 amyloid deposition is found in meningocortical blood vessels and in diffuse plaques in the cerebral cortex. Diffuse plaques putatively represent early stages in the formation of senile plaques. Microglia are intimately associated with congophilic plaques in Alzheimer's disease (AD), but microglial involvement in diffuse plaque formation is controversial. Therefore, we studied the relationship between microglia and diffuse plaques in the cerebral cortex of four patients with HCHWA-D using a panel of macrophage/microglia markers (mAbs LCA, LeuM5, LeuM3, LN3, KP1, OKIa, CLB54, Mac1, Ki-M6, AMC30 and the lectin RCA-1). Eight AD patients, one demented Down's syndrome (DS) patient and four non-demented controls were included for comparison. In controls and HCHWA-D patients ramified or "resting" microglia formed a reticular array in cortical gray and subcortical white matter. Microglial cells in or near HCHWA-D diffuse plaques retained their normal regular spacing and ramified morphology. In AD/DS gray matter more microglial cells were stained than in controls and HCHWA-D patients. Intensely immunoreactive microglia with enlarged cell bodies and short, thick processes clustered in congophilic plaques. In contrast to the resting microglia, these "activated microglia" strongly expressed class II major histocompatibility complex antigen, HLA-DR, and were AMC30-immunoreactive. These findings support the view that microglia play a role in the formation of congophilic plaques but do not initiate diffuse plaque formation. Another finding in this study is the presence of strong monocyte/macrophage marker immunoreactivity in the wall of cortical congophilic blood vessels in HCHWA-D.
在遗传性脑出血伴淀粉样变性（荷兰型）（HCHWA-D）中，β/A4淀粉样蛋白沉积见于脑膜皮质血管和大脑皮质的弥漫性斑块中。弥漫性斑块可能代表老年斑形成的早期阶段。小胶质细胞与阿尔茨海默病（AD）中的嗜刚果红性斑块密切相关，但小胶质细胞在弥漫性斑块形成中的作用存在争议。因此，我们使用一组巨噬细胞/小胶质细胞标志物（单克隆抗体LCA、LeuM5、LeuM3、LN3、KP1、OKIa、CLB54、Mac1、Ki-M6、AMC30和凝集素RCA-1）研究了4例HCHWA-D患者大脑皮质中小胶质细胞与弥漫性斑块之间的关系。纳入8例AD患者、1例痴呆唐氏综合征（DS）患者和4例非痴呆对照进行比较。在对照组和HCHWA-D患者中，分支状或“静息”小胶质细胞在皮质灰质和皮质下白质中形成网状排列。HCHWA-D弥漫性斑块内或附近的小胶质细胞保持其正常的规则间距和分支形态。在AD/DS灰质中，染色的小胶质细胞比对照组和HCHWA-D患者更多。细胞体增大、突起短而粗的强免疫反应性小胶质细胞聚集在嗜刚果红性斑块中。与静息小胶质细胞不同，这些“活化小胶质细胞”强烈表达II类主要组织相容性复合体抗原HLA-DR，且对AMC30呈免疫反应性。这些发现支持了小胶质细胞在嗜刚果红性斑块形成中起作用但不启动弥漫性斑块形成的观点。本研究的另一个发现是HCHWA-D患者皮质嗜刚果红性血管壁中存在强单核细胞/巨噬细胞标志物免疫反应性。
