4.5 Article

Immunohistochemical Visualization of Amyloid-beta Protein Precursor and Amyloid-beta in Extra- and Intracellular Compartments in the Human Brain

期刊

JOURNAL OF ALZHEIMERS DISEASE
卷 20, 期 4, 页码 1015-1028

出版社

IOS PRESS
DOI: 10.3233/JAD-2010-091681

关键词

Amyloid-beta; immunohistochemistry; intracellular; postmortem brain

资金

  1. European Union [LSHM-CT-2004-503039]
  2. Finnish Cultural Foundation
  3. Health Research Council of the Academy of Finland
  4. Kuopio University Hospital [5772708]
  5. Nordic Centre of Excellence of Neurodegeneration

向作者/读者索取更多资源

Amyloid-beta (A beta) peptide, a cleavage product of the amyloid-beta protein precursor (A beta PP), has been reported to be detected in the intracellular compartment. Most studies reporting the presence of intracellular A beta are based on the use of immunohistochemistry. In this study, the presence of A beta PP and A beta was assessed by applying immunohistochemistry in postmortem human brain tissue samples obtained from 10 neurologically intact subjects, the youngest being 2 years of age, one aged with mild cognitive impairment, 14 neurologically diseased, and in one brain biopsy sample obtained from a subject with normal pressure hydrocephalus. Intracellular immunoreactivity was detected in all ages independent of the disease state or existence of extracellular A beta aggregates with all antibodies directed to A beta PP, with three A beta antibodies (4G8, 6E10, and 82E1), clones that are unable to distinguish A beta from A beta PP. These results suggest that it is A beta PP rather than A beta that is detected intracellularly when using the antibodies listed above. Furthermore, the staining results varied when different pretreatment strategies were applied. Interestingly intracellular A beta was detected with antibodies directed to the C-terminus of A beta (neoepitope) in subjects with Alzheimer's disease. The lack of intracellular immunoreactivity in unimpaired subjects, when using antibodies against neoepitopes, may be due to a lack or a low level of the protein that is thus undetectable at light microscopic level by immunohistochemistry method. The staining results and conclusions depended strongly on the chosen antibody and the pretreatment strategy and thus multiple antibodies must be used when assessing the intracellular accumulation of A beta.

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。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据