Granulovacuolar degeneration bodies of Alzheimer's disease resemble late‐stage autophagic organelles

Abstract

Granulovacuolar degeneration involves the accumulation of large, double membrane‐bound bodies within certain neurons during the course of Alzheimer's disease. Because of the two‐layer membrane morphology, it has been proposed that the bodies are related to autophagic organelles. To test this hypothesis, spatial colocalization of autophagic and endocytic markers with casein kinase 1 delta, a marker for granulovacuolar degeneration bodies (GVBs), was investigated in hippocampal sections prepared from post mortem Alzheimer's disease cases using double‐label confocal fluorescence microscopy. Results revealed that GVBs colocalized most strongly with LAMP1 (lysosome‐associated membrane protein 1) and CHMP2B (charged multivesicular body protein 2B), but weakly with lysosomal marker cathepsin D or early‐stage autophagy markers LC3 and p62. The resultant immunohistochemical signature suggests that 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. This work was supported in part by the National Institute on Aging (AG14452, JK).