Lidström A M, Bogdanovic N, Hesse C, Volkman I, Davidsson P, Blennow K
Department of Clinical Neuroscience, Göteborg University, Sahlgrenska University Hospital, M olndal, Sweden.
Exp Neurol. 1998 Dec;154(2):511-21. doi: 10.1006/exnr.1998.6892.
We studied the multifunctional protein clusterin (apolipoprotein J, SGP-2, SP-40,40) in brain tissue using quantitative Western blotting and immunohistochemistry. The material included postmortem brains from 19 patients with Alzheimer's disease (AD), 6 with vascular dementia (VAD), and 7 age-matched control subjects. Intense clusterin staining was found in the soma of both neuronal and astroglial cells. In addition, positive staining was found in a portion of senile plaques (SP) in AD brains. Quantitative analysis showed that clusterin levels were significantly increased in AD, both in frontal cortex (150% of the control value, P = 0.002) and in the hippocampus (179% of the control value, P < 0.001), while normal clusterin levels were found in cerebellum (104% of the control value). No significant changes were found in VAD. Within the AD group, there was a significant negative correlation between clusterin levels in hippocampus and severity of dementia (r = -0.40), while no such correlation was found in frontal cortex (r = 0.12). No significant correlations were found between clusterin levels and the number of SP or neurofibrillary tangles. No significant differences in clusterin levels were found in any brain region between AD patients possessing different numbers of the ApoE4 allele. The increased clusterin levels in AD brain, together with the absence of a correlation between SP counts and clusterin levels, and the finding that clusterin is only found in a smaller portion of SP do not suggest a link between clusterin and beta-amyloid dependence. Instead we hypothesize that the increase is part of a regional response in AD brain.
我们使用定量蛋白质免疫印迹法和免疫组织化学方法研究了脑组织中的多功能蛋白簇集蛋白（载脂蛋白J、SGP-2、SP-40,40）。研究材料包括19例阿尔茨海默病（AD）患者、6例血管性痴呆（VAD）患者以及7例年龄匹配的对照者的死后大脑。在神经元和星形胶质细胞的胞体中均发现了强烈的簇集蛋白染色。此外，在AD大脑的一部分老年斑（SP）中也发现了阳性染色。定量分析显示，AD患者额叶皮质（为对照值的150%，P = 0.002）和海马体（为对照值的179%，P < 0.001）中的簇集蛋白水平显著升高，而小脑的簇集蛋白水平正常（为对照值的104%）。VAD患者未发现显著变化。在AD组中，海马体中的簇集蛋白水平与痴呆严重程度之间存在显著负相关（r = -0.40），而额叶皮质中未发现这种相关性（r = 0.12）。簇集蛋白水平与SP数量或神经原纤维缠结之间未发现显著相关性。在具有不同数量ApoE4等位基因的AD患者之间，任何脑区的簇集蛋白水平均未发现显著差异。AD大脑中簇集蛋白水平升高，以及SP计数与簇集蛋白水平之间缺乏相关性，且仅在一小部分SP中发现簇集蛋白，这些均不表明簇集蛋白与β-淀粉样蛋白依赖性之间存在联系。相反，我们推测这种升高是AD大脑区域反应的一部分。
