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Aims  Among the pathological findings in  A lzheimer's disease ( AD ), the temporal and spatial profiles of granulovacuolar degeneration ( GVD ) bodies are characteristic in that they seem to be related to those of neurofibrillary tangles ( NFT s), suggesting a common mechanism underlying the pathogenesis of these structures. Flotillin‐1, a marker of lipid rafts, accumulates in lysosomes of tangle‐bearing neurones in  AD  patients. In addition, recent reports have shown that  GVD  bodies accumulate at the nexus of the autophagic and endocytic pathways. The aim of this study was to elucidate the distribution of the lipid component of lipid rafts, phosphatidylinositol‐4,5‐bisphosphate [ P td I ns(4,5) P 2], in  AD  and other neurodegenerative disorders.    Methods  We compared  P td I ns(4,5) P 2 immunoreactivity in the hippocampus, entorhinal cortex and neocortex of five  AD  cases, 17 cases of other neurodegenerative disorders and four controls. In addition, we performed double staining using markers of  GVD ,  NFT s and lipid rafts for further characterization.    Results  Immunohistochemical analysis revealed that  P td I ns(4,5) P 2 was selectively enriched in  GVD  bodies and  NFT s. Although immunoreactivity for  P td I ns(4,5) P 2 was also evident in  NFT s composed of hyperphosphorylated tau,  P td I ns(4,5) P 2 was segregated from phosphorylated tau within  NFT s by double immunofluorescence staining. In contrast,  P td I ns(4,5) P 2 colocalized with the lipid raft markers flotillin‐1 and annexin 2, within  GVD  bodies and  NFT s.    Conclusions  These results suggest that lipid raft components including  P td I ns(4,5) P 2 play a role in the formation of both  GVD  bodies and  NFT s.

Phosphatidylinositol‐4,5‐bisphosphate is enriched in granulovacuolar degeneration bodies and neurofibrillary tangles