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.

Imaging as a strategy for premortem diagnosis and staging of tauopathies.

Alzheimer's disease is diagnosed by postmortem detection of pathological lesions that accumulate in specific brain regions. Although the presence of both beta-amyloid plaques and tau-bearing neurofibrillary lesions defines Alzheimer's disease, the distribution of neurofibrillary lesions alone correlates strongly with neurodegeneration and cognitive decline. A whole-brain imaging test capable of detecting these lesions in premortem cases could have great potential for staging and differentially diagnosing Alzheimer's disease. Here we discuss the challenges in developing a whole-brain imaging approach for detection of this intracellular target.