Author declaration: None of the authors listed above has declared any conflict of interest within the last 3 years which may arise from being named as an author on this manuscript.
Granulovacuolar degeneration (GVD) bodies of Alzheimer's disease (AD) resemble late-stage autophagic organelles
Article first published online: 22 FEB 2011
© 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 37, Issue 3, pages 295–306, April 2011
How to Cite
Funk, K. E., Mrak, R. E. and Kuret, J. (2011), Granulovacuolar degeneration (GVD) bodies of Alzheimer's disease (AD) resemble late-stage autophagic organelles. Neuropathology and Applied Neurobiology, 37: 295–306. doi: 10.1111/j.1365-2990.2010.01135.x
- Issue published online: 22 FEB 2011
- Article first published online: 22 FEB 2011
- Accepted manuscript online: 14 OCT 2010 10:08PM EST
- Received 8 July 2010, Accepted after revision 28 September 2010, Published online Article Accepted on 14 October 2010
- Alzheimer's disease;
- granulovacuolar degeneration;
K. E. Funk, R. E. Mrak and J. Kuret (2011) Neuropathology and Applied Neurobiology37, 295–306 Granulovacuolar degeneration (GVD) bodies of Alzheimer's disease (AD) resemble late-stage autophagic organelles
Aims: Granulovacuolar degeneration involves the accumulation of large, double membrane-bound bodies within certain neurones during the course of Alzheimer's disease (AD) and other adult-onset 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 stalls in AD. Methods: Spatial colocalization of autophagic and endocytic markers with casein kinase 1 delta, a marker for granulovacuolar degeneration (GVD) bodies, was evaluated in hippocampal sections prepared from post mortem Braak stage IV and V AD cases using double-label confocal fluorescence microscopy. Results: GVD bodies colocalized weakly with early-stage autophagy markers LC3 and p62, but strongly with late-stage marker lysosome-associated membrane protein 1 (LAMP1), which decorated their surrounding membranes. GVD bodies also colocalized strongly with charged multivesicular body protein 2B (CHMP2B), which colocalized with the core granule, but less strongly with lysosomal marker cathepsin D. Conclusions: The resultant immunohistochemical signature suggests that granulovacuolar degeneration bodies (GVBs) do 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 GVB accumulation.