Abstract:
Amyloid beta (Aβ) plaques are one of the hallmarks of Alzheimer\'s disease (AD). However, currently available anti-amyloid therapies fail to show effectiveness in the treatment of AD in humans. It has been found that there are different types of Aβ plaque (diffuse and focal types) in the postmortem human brain. In this study, we aimed to investigate the correlations among different types of Aβ plaque and AD-related neuropathological and cognitive changes based on a postmortem human brain bank in China. The results indicated that focal plaques, but not diffuse plaques, significantly increased with age in the human hippocampus. We also found that the number of focal plaques was positively correlated with the severity of AD-related neuropathological changes (measured by the \"ABC\" scoring system) and cognitive decline (measured by the Everyday Cognitive Insider Questionnaire). Furthermore, most of the focal plaques were co-localized with neuritic plaques (identified by Bielschowsky silver staining) and accompanied by microglial and other inflammatory cells. Our findings suggest the potential of using focal-type but not general Aβ plaques as biomarkers for the neuropathological evaluation of AD.
摘要:
淀粉样β(Aβ)斑块是阿尔茨海默病(AD)的标志之一。然而,目前可用的抗淀粉样蛋白疗法未能显示出治疗人类AD的有效性。已经发现,死后人脑中存在不同类型的Aβ斑块(弥散型和局灶型)。在这项研究中,我们的目的是研究不同类型的Aβ斑块与AD相关的神经病理学和认知改变之间的相关性。结果表明,局灶性斑块,但不是弥漫性斑块,随着年龄的增长,人类海马体显著增加。我们还发现,局灶性斑块的数量与AD相关神经病理学改变(通过“ABC”评分系统测量)和认知下降(通过日常认知内幕问卷测量)的严重程度呈正相关。此外,大多数局灶性斑块与神经炎性斑块共定位(通过Bielschowsky银染鉴定),并伴有小胶质细胞和其他炎性细胞.我们的发现表明,使用局灶型而不是一般Aβ斑块作为AD的神经病理学评估的生物标志物的潜力。