Buée L, Hof P R, Bouras C, Delacourte A, Perl D P, Morrison J H, Fillit H M
Department of Geriatrics and Adult Development, Mount Sinai Medical Center, New York, NY 10029-6574.
Acta Neuropathol. 1994;87(5):469-80. doi: 10.1007/BF00294173.
Alterations of the cerebral microvasculature have been reported in aging and in neurodegenerative disorders such as Alzheimer's disease. However, the exact role of microvascular alterations in the pathogenesis of neurodegeneration remains unknown. In the present report, the cerebral cortex microvasculature was studied by immunohistochemistry using a monoclonal antibody against vascular heparan sulfate proteoglycan protein core in normal aging controls. Alzheimer's disease, Down syndrome, Guam amyotrophic lateral sclerosis/parkinsonian dementia complex, Pick's disease and dementia pugilistica. In all dementing illnesses, increased microvascular pathology was evident compared to normal controls. Decreased microvascular density and numerous atrophic vessels were the primary abnormalities observed in all dementing disorders. These microvascular abnormalities demonstrated regional and laminar selectivity, and were primarily found in layers III and V of frontal and temporal cortex. Quantitative analysis employing computer-assisted microscopy demonstrated that the decrease in microvascular density in Alzheimer's disease was statistically significant compared to age-matched controls. In addition, extracellular heparan sulfate proteoglycan deposits were observed which colocalized with thioflavine S-positive senile plaques in Alzheimer's disease, Down syndrome and selected Guam dementia cases. In some cases, heparan sulfate proteoglycan was seen in senile plaques that appeared to be diffuse or primitive plaques that stained weakly with thioflavine. Heparan sulfate proteoglycan-containing neurons were also observed in Alzheimer's disease, as well as in Down syndrome and Guam cases. Glial staining for heparan sulfate proteoglycan was never observed. Our data support previous observations that microvascular pathology is found in aging and in Alzheimer's disease. The changes in Alzheimer's disease exceed those found in normal aging controls. We also found microvascular pathology in all other dementing disorders studied. Our studies further demonstrated that the microvascular pathology displays regional and laminar patterns which parallel patterns of neuronal loss. Finally, we also found that heparan sulfate proteoglycan is present in senile plaques and neurons not only as previously reported in Alzheimer's disease, but also in Down syndrome and Guam cases. Heparan sulfate proteoglycan in senile plaques may be derived from either the degenerating microvasculature or from degenerating neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
在衰老以及诸如阿尔茨海默病等神经退行性疾病中，已报道存在脑微血管的改变。然而，微血管改变在神经退行性变发病机制中的确切作用仍不清楚。在本报告中，通过免疫组织化学方法，使用抗血管硫酸乙酰肝素蛋白聚糖蛋白核心的单克隆抗体，对正常衰老对照、阿尔茨海默病、唐氏综合征、关岛肌萎缩侧索硬化/帕金森痴呆综合征、匹克病和拳击性痴呆患者的大脑皮质微血管进行了研究。在所有痴呆性疾病中，与正常对照相比，微血管病变均明显增加。微血管密度降低和大量萎缩血管是在所有痴呆性疾病中观察到的主要异常。这些微血管异常表现出区域和层状选择性，主要见于额叶和颞叶皮质的Ⅲ层和Ⅴ层。采用计算机辅助显微镜进行的定量分析表明，与年龄匹配的对照相比，阿尔茨海默病中微血管密度的降低具有统计学意义。此外，在阿尔茨海默病、唐氏综合征和部分关岛痴呆病例中，观察到细胞外硫酸乙酰肝素蛋白聚糖沉积物与硫黄素S阳性老年斑共定位。在某些情况下，在似乎是弥漫性或原始的、硫黄素染色较弱的老年斑中可见硫酸乙酰肝素蛋白聚糖。在阿尔茨海默病以及唐氏综合征和关岛病例中，也观察到含有硫酸乙酰肝素蛋白聚糖的神经元。从未观察到硫酸乙酰肝素蛋白聚糖的胶质细胞染色。我们的数据支持先前的观察结果，即在衰老和阿尔茨海默病中存在微血管病变。阿尔茨海默病中的变化超过了正常衰老对照中的变化。我们还在所有其他研究的痴呆性疾病中发现了微血管病变。我们的研究进一步表明，微血管病变呈现出与神经元丢失模式平行的区域和层状模式。最后，我们还发现，硫酸乙酰肝素蛋白聚糖不仅如先前在阿尔茨海默病中所报道的那样存在于老年斑和神经元中，在唐氏综合征和关岛病例中也存在。老年斑中的硫酸乙酰肝素蛋白聚糖可能来源于退化的微血管或退化的神经元。（摘要截选至400字）
