IMMUNOHISTOCHEMICAL EXAMINATION OF PHOSPHORYLATED TAU IN GRANULOVACUOLAR DEGENERATION GRANULES

Granulovacuolar degeneration (GVD) and neurofibrillary tangles (NFT) a re neuropathological features in Alzheimer's disease (AD). The molecul ar mechanism of GVD formation remains unknown. Recent immunohistochemi cal investigations suggested a potential link of NFT to GVD formation. Enzyme histochemical studies and electronmicroscopic findings suggest ed that GVD is formed through lysosomal autophagy of intraneuronal sub stances. We recently demonstrated that in non-demented cases NFT was p hosphorylated at serines 199, 202 and 422 in paired helical filament ( PHF)-tau more than in serine 396, while NFT in AD cases was similarly phosphorylated at these four sites in tau. In this study, we demonstra ted immunohistochemically a similar phosphorylation state of tau in GV D granules to that in NFT in both non-demented cases and AD patients b y using a mouse monoclonal anti-tau antibody and three phosphorylation site-specific antibodies for PHF-tau, indicating that GVD granules an d NFT are composed of similar phosphorylated-tau. However, we could no t detect PHF structures within ally GVD using electronmicroscopy, indi cating that PHF itself is not phagocytized by lysosomes during GVD for mation. Therefore, the source of GVD granules might be phosphorylated pre-PHF-tau.