Granulovacuolar degeneration (GVD) bodies of Alzheimer's disease (AD) resemble late-stage autophagic organelles.
Granulovacuolar degeneration (GVD) bodies of Alzheimer's disease (AD) resemble late-stage autophagic organelles.
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DOI：
10.1111/j.1365-2990.2010.01135.x
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发表时间：
2011-04
影响因子：
5
通讯作者：
Kuret J
中科院分区：
文献类型：
--
作者：
Funk KE;Mrak RE;Kuret J
颗粒泡变性包括在阿尔茨海默病和其他成人型痴呆的过程中，某些神经元内积累的大的、双膜结合的小体。由于双层膜的形态，有人认为这些小体与自噬细胞器有关。这项研究的目的是检验这一假说，并确定阿尔茨海默病中该通路停滞的大致阶段。用双标记共聚焦荧光显微镜观察了Braak IV期和V期阿尔茨海默病尸检标本的海马区切片中，自噬和内吞标记与GVD小体标记酪蛋白激酶1的空间共定位。GVD小体与早期自噬标记Lc3和P62弱共存，但与装饰其周围膜的晚期标记LAMP1(溶酶体相关膜蛋白1)强烈共存。GVD小体还与CHMP2B(带电多囊泡体蛋白2B)强烈共定位，CHMP2B与核心颗粒共定位，但与溶酶体标记组织蛋白D的共定位较弱。由此产生的免疫组织化学特征表明，GVD小体含有晚期自噬标记，并聚集在自噬和内吞通路的连接处。。数据进一步表明，未能完成自溶酶体的形成可能是GVD小体积聚的一个重要相关因素。
Granulovacuolar degeneration involves the accumulation of large, double membrane-bound bodies within certain neurons during the course of Alzheimer’s disease and other adultonset dementias. Because of the two-layer membrane morphology, it has been proposed that the bodies are related to autophagic organelles. The aim of this study was to test this hypothesis, and determine the approximate stage at which the pathway stalled in Alzheimer’s disease. Spatial colocalization of autophagic and endocytic markers with casein kinase 1 delta, a marker for GVD bodies, was evaluated in hippocampal sections prepared from postmortem Braak stage IV and V Alzheimer’s disease cases using double-label confocal fluorescence microscopy. GVD bodies colocalized weakly with early-stage autophagy markers LC3 and p62, but strongly with late-stage marker LAMP1 (lysosome-associated membrane protein 1), which decorated their surrounding membranes. GVD bodies also colocalized strongly with CHMP2B (charged multivesicular body protein 2B), which colocalized with the core granule, but less strongly with lysosomal marker cathepsin D. The resultant immunohistochemical signature suggests that GVD bodies contain late-stage autophagic markers, and accumulate at the nexus of autophagic and endocytic pathways. . The data further suggest that failure to complete autolysosome formation may be an important correlate of GVD body accumulation.
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