Vinters H V, Nishimura G S, Secor D L, Pardridge W M
Department of Pathology (Neuropathology), UCLA School of Medicine 90024-1732.
Am J Pathol. 1990 Aug;137(2):233-40.
Cerebral amyloid angiopathy (CAA) defines a biochemically heterogeneous entity that manifests as effacement of cerebral microvessel walls by a fibrillar material with characteristic tinctorial properties. In biochemical terms, the amyloid that infiltrates blood vessels in CAA is composed of the A4 or beta peptide of Alzheimer's disease (AD), a molecule related to gamma trace or cystatin C (seen in patients with hereditary cerebral hemorrhage with amyloidosis in Iceland, HCHWA-I), or the PrP characteristic of spongiform encephalopathy and scrapie. Using antibodies to synthetic peptides representing portions of the 4.2-kd Alzheimer A4 peptide and the gamma-trace peptide, we immunostained sections of brain from patients with AD, senile dementia of Alzheimer's type, and CAA with associated leukoencephalopathy. Immunohistochemical studies demonstrated colocalization of the A4 and gamma-trace peptides within arteriolar walls, but only rarely in A4 amyloidotic capillaries or senile plaque cores of amyloid. When gamma-tracelike reactivity was noted in capillary walls, it was sometimes noted within the cytoplasm of pericytes. Immunostaining was always more intense when the anti-A4 antibody was used as the primary antibody. Gamma-trace immunostaining was more prominent on the adventitial component of arteriolar walls, whereas A4 staining was usually seen more diffusely throughout the blood vessel wall, especially in the media. Rarely individual pericytelike cells showed prominent gamma-trace immunoreactivity. These findings suggest that A4 and gamma-tracelike molecules may colocalize within arteriolar walls within the brains of patients with AD, and highlight the fact that CAA identified with AD and HCHWA-I are not as biochemically distinct as was assumed previously. Furthermore these findings suggest that other peptidases or protease inhibitors may be found within amyloidotic microvessel walls and may contribute to senile brain change and CAA-related strokes, including hemorrhage and encephalomalacia.
脑淀粉样血管病（CAA）是一种生化性质异质性的疾病，其表现为脑微血管壁被具有特征性染色特性的纤维状物质所取代。从生化角度来看，CAA中浸润血管的淀粉样蛋白由阿尔茨海默病（AD）的A4或β肽、与γ-微量蛋白或胱抑素C相关的分子（见于冰岛遗传性脑出血伴淀粉样变性患者，HCHWA-I）或海绵状脑病和羊瘙痒病的PrP组成。我们使用针对代表4.2kd阿尔茨海默A4肽和γ-微量蛋白肽部分的合成肽的抗体，对AD患者、阿尔茨海默型老年痴呆患者以及伴有白质脑病的CAA患者的脑切片进行免疫染色。免疫组织化学研究表明，A4和γ-微量蛋白肽在小动脉壁内共定位，但在A4淀粉样变性毛细血管或淀粉样老年斑核心中很少见。当在毛细血管壁中发现γ-微量蛋白样反应性时，有时在周细胞的细胞质中也能看到。当以抗A4抗体作为一抗时，免疫染色总是更强。γ-微量蛋白免疫染色在小动脉壁的外膜成分上更突出，而A4染色通常在整个血管壁中更弥散，尤其是在中膜。很少有单个周细胞样细胞显示出明显的γ-微量蛋白免疫反应性。这些发现表明，A4和γ-微量蛋白样分子可能在AD患者脑内的小动脉壁中共定位，并突出了这样一个事实，即与AD和HCHWA-I相关的CAA在生化上并不像以前认为的那样截然不同。此外，这些发现表明，在淀粉样变性微血管壁中可能发现其他肽酶或蛋白酶抑制剂，它们可能导致老年脑变化和与CAA相关的中风，包括出血和脑软化。
