期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 158, 期 1, 页码 189-198出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/S0002-9440(10)63957-0
关键词
-
类别
资金
- NIA NIH HHS [R01 AG012694, 5T32AG00096, R37 AG012694, AG12694, 5R01AG13007, T32 AG000096] Funding Source: Medline
- NATIONAL INSTITUTE ON AGING [R37AG012694, T32AG000096, R01AG013007, R01AG012694] Funding Source: NIH RePORTER
Although evidence suggests that neurofibrillary tangles (NFTs) and neuronal tell loss are prominent features of Alzheimer's disease (AD), the relationship between the two remains unknown. In the present study, the relationship between the activation of apoptotic mechanisms and NFT formation in AD was investigated using a caspase-cleavage site-directed antibody to fodrin, an abundant neuronal cytoskeleton protein. This antibody recognized cleavage products of fodrin after digestion by caspase-3, but did not recognize full-length fodrin. Itt vitro analysis of this fodrin caspase-cleavage product (CCP) antibody demonstrates that it is a specific probe for the detection of apoptotic but not necrotic pathways in cultured neurons. To determine whether caspases cleave fodrin in vivo, tissue sections from controls and AD were immunostained for fodrin (CCPs). Although no staining was observed in control cases, labeling of neurons was observed in the hippocampus of all AD cases, which increased as a function of disease progression. To determine a possible relationship between caspase activation and NFT formation, double-labeling experiments with fodrin CCP and PHF-1 were performed. Co-localization of these markers was observed in many neurons, and quantitative analysis showed that as the extent of NFT formation increased, there was a significant corresponding increase in fodrin CCP immunolabeling (r = 0.84). Taken together, these results provide evidence for the activation of apoptotic mechanisms in neurons in the AD brain and suggest that there is an association between NFT formation and the activation of apoptotic pathways in AD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据