Schipper H M, Cissé S
Bloomfield Centre for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis, Jewish General Hospital, Montreal, Quebec, Canada.
Glia. 1995 May;14(1):55-64. doi: 10.1002/glia.440140108.
Corpora amylacea (CA) are cytoplasmic inclusions that accumulate in human brain in the course of normal aging, and to an even greater extent, in Alzheimer's disease and other neurodegenerative conditions. In senescent and Alzheimer-diseased human brains, astrocytes in limbic and periventricular regions exhibit red autofluorescent inclusions, homologous to Gomori-positive astrocyte granules previously described in the brains of aging rodents and other vertebrates. We have shown that Gomori inclusions in situ and in culture are derived from autophagocytosed mitochondria exhibiting iron-mediated peroxidase activity. In the human brain, the autofluorescent inclusions share many properties with CA. Both types of inclusion progressively accumulate in periventricular regions with advancing age, are largely astrocytic in origin, and contain various heat shock proteins and ubiquitin. Using histochemistry in conjunction with cofocal microscopy, we demonstrated that both CA and the red autofluorescent granules exhibit non-enzymatic peroxidase activity and an affinity for CAH and PAS. The only major divergent histochemical feature between the Gomori-positive astrocyte granules and CA is the presence of orange-red autofluorescence in the former and the absence of endogenous fluorescence in the latter. On the basis of numerous shared topographic and histochemical features, we hypothesized that CA are largely derived from autofluorescent (Gomori-positive) astrocyte granules which reside in periventricular regions of the senescent CNS. Immunofluorescent labeling and laser scanning confocal microscopy demonstrated consistent colocalization of the mitochondrial proteins, sulfite oxidase, and heat shock protein 60, to both CA and the autofluorescent astroglial inclusions. In addition, both CA and the autofluorescent astrocyte granules exhibit staining for DNA which colocalizes to mitochondrial antigens and therefore likely represents mitochondrial nucleic acid in dual-labeled preparations. These observations suggest that a) Gomori-positive astrocyte granules in human brain are homologous to those described in rodents, b) Gomori-positive granules may be structural precursors of CA in senescent human brain, and c) in the aging human brain, degenerate mitochondria within periventricular astrocytes give rise to autofluorescent cytoplasmic granules and corpora amylacea.
淀粉样体（CA）是在正常衰老过程中在人脑中积累的细胞质内含物，在阿尔茨海默病和其他神经退行性疾病中积累程度更高。在衰老和患阿尔茨海默病的人脑中，边缘和脑室周围区域的星形胶质细胞呈现红色自发荧光内含物，与先前在衰老啮齿动物和其他脊椎动物脑中描述的Gomori阳性星形胶质细胞颗粒同源。我们已经表明，原位和培养中的Gomori内含物源自表现出铁介导的过氧化物酶活性的自噬线粒体。在人脑中，自发荧光内含物与CA具有许多共同特性。两种类型的内含物都随着年龄的增长在脑室周围区域逐渐积累，主要起源于星形胶质细胞，并含有各种热休克蛋白和泛素。使用组织化学结合共聚焦显微镜，我们证明CA和红色自发荧光颗粒都表现出非酶促过氧化物酶活性以及对CAH和PAS的亲和力。Gomori阳性星形胶质细胞颗粒和CA之间唯一主要的不同组织化学特征是前者存在橙红色自发荧光，而后者不存在内源性荧光。基于众多共同的地形和组织化学特征，我们假设CA主要源自存在于衰老中枢神经系统脑室周围区域的自发荧光（Gomori阳性）星形胶质细胞颗粒。免疫荧光标记和激光扫描共聚焦显微镜显示线粒体蛋白、亚硫酸盐氧化酶和热休克蛋白60在CA和自发荧光星形胶质细胞内含物中一致共定位。此外，CA和自发荧光星形胶质细胞颗粒都显示出对DNA的染色，该染色与线粒体抗原共定位，因此在双标记制剂中可能代表线粒体核酸。这些观察结果表明：a）人脑中的Gomori阳性星形胶质细胞颗粒与啮齿动物中描述的颗粒同源；b）Gomori阳性颗粒可能是衰老人类大脑中CA的结构前体；c）在衰老的人类大脑中，脑室周围星形胶质细胞内退化的线粒体产生自发荧光细胞质颗粒和淀粉样体。
