Possible neuroprotective role of clusterin in Alzheimer's disease:: A quantitative immunocytochemical study

被引:78
作者
Giannakopoulos, P [1 ]
Kövari, E
French, LE
Viard, I
Hof, PR
Bouras, C
机构
[1] HUG Belle Idee, Psychiat Clin 1, CH-1225 Geneva, Switzerland
[2] Univ Geneva, Sch Med, Dept Psychiat, CH-1225 Geneva, Switzerland
[3] HUG Belle Idee, Div Neuropsychiat, CH-1225 Geneva, Switzerland
[4] Univ Geneva, Sch Med, Dept Dermatol, CH-1211 Geneva 14, Switzerland
[5] CUNY Mt Sinai Sch Med, Neurobiol Aging Labs, New York, NY 10029 USA
[6] CUNY Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA
[7] CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA
[8] CUNY Mt Sinai Sch Med, Dept Ophthalmol, New York, NY 10029 USA
关键词
Alzheimer's disease; cerebral cortex; clusterin; neurofibrillary tangle; neuronal loss;
D O I
10.1007/s004010050815
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Clusterin is a secreted glycoprotein that is expressed in response to tissue injury both in peripheral organs and in the brain. Recent studies have shown a substantial increase in clusterin mRNA in pyramidal neurons of the hippocampus and the entorhinal cortex in Alzheimer's disease (AD), with clusterin immunoreactivity occurring in neuropil threads, neurofibrillary tangles (NFT), and senile plaques. To elucidate further the role of this protein in the degenerative process, a quantitative study of its distribution in the cerebral cortex of non-demented and AD patients, all older than 85 years of age, was performed using immunocytochemistry. Using a stereological approach, we found that in cortical areas affected in AD, such as the entorhinal, inferior temporal and superior frontal cortices, the percentage of NFT-free neurons displaying clusterin immunoreactivity was significantly higher than that in non-demented cases. No such increase in the density of clusterin-immunoreactive neurons was seen in cortical areas that were less affected in the disease process. Furthermore, clusterin immunoreactivity was rarely observed in NFT-containing neurons. In conjunction with previous observations in peripheral tissues, these data suggest that clusterin may have a neuroprotective role, and that in AD, low cellular expression of this protein may be associated with neuronal degeneration and death.
引用
收藏
页码:387 / 394
页数:8
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