Miyakawa T, Kimura T, Hirata S, Fujise N, Ono T, Ishizuka K, Nakabayashi J
Department of Neuropsychiatry, Kumamoto University School of Medicine, Japan.
Ann N Y Acad Sci. 2000 Apr;903:46-54. doi: 10.1111/j.1749-6632.2000.tb06349.x.
Vascular factors have been shown to be highly involved in the deposition of the amyloid beta-protein (A beta) in the brain of Alzheimer's disease (AD). However, the detailed mechanism remains unknown. Here, we showed that more numerous deposits of A beta 40 and A beta 42 in the brain were found in AD patients than in controls. Together with evidence of no difference in the level of A beta 40 and A beta 42 in sera between sporadic AD and controls, a certain dysfunction of the blood-brain barrier could induce an abnormal transport of A beta from sera to the parenchyma in AD. In addition, vascular A beta deposits and mature A beta plaques stained by Congo red in AD brains contained more A beta 40 than A beta 42, whereas Congo red-negative immature plaques mainly consisted of A beta 42. Our confocal laser scanning microscopy demonstrated an intimate relationship between A beta 40 and the vascular network. The amount of mature plaques but not that of immature plaques was reportedly correlated with the severity of dementia in AD patients. These results suggest that serum-derived A beta 40 and/or A beta 42 cause A beta 40 deposition in and around blood vessels through unknown but possible mechanisms such as (1) endocytosis of A beta 40, (2) selective transport A beta 40 and A beta 42 into blood vessels and the parenchyma, respectively, and (3) proteolysis of A beta 42 into A beta 40 induced by a putative carboxyl dipeptidase in blood vessels including vascular feet, which is involved in A beta fibrillation and cognitive deterioration in the patients. Therefore, the accumulation of A beta 40 associated with blood vessels may play a critical role in the development of AD.
血管因素已被证明与阿尔茨海默病（AD）患者大脑中β淀粉样蛋白（Aβ）的沉积密切相关。然而，具体机制仍不清楚。在此，我们发现，与对照组相比，AD患者大脑中Aβ40和Aβ42的沉积更多。同时，散发性AD患者血清中Aβ40和Aβ42水平与对照组无差异，提示血脑屏障功能异常可能导致AD患者血清中Aβ异常转运至脑实质。此外，AD患者大脑中经刚果红染色的血管Aβ沉积物和成熟Aβ斑块所含Aβ40多于Aβ42，而刚果红阴性的未成熟斑块主要由Aβ42组成。我们的共聚焦激光扫描显微镜显示Aβ40与血管网络密切相关。据报道，AD患者成熟斑块的数量而非未成熟斑块的数量与痴呆严重程度相关。这些结果表明，血清来源的Aβ40和/或Aβ42通过未知但可能的机制导致血管内及周围Aβ40沉积，这些机制包括：（1）Aβ40的内吞作用；（2）分别将Aβ40和Aβ42选择性转运至血管和脑实质；（3）血管（包括血管足）中假定的羧基二肽酶将Aβ42蛋白水解为Aβ40，这与患者的Aβ纤维化和认知功能恶化有关。因此，与血管相关的Aβ40积累可能在AD的发展中起关键作用。
