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Phosphatidylinositol‐4,5‐bisphosphate is enriched in granulovacuolar degeneration bodies and neurofibrillary tangles
Author(s) -
Nishikawa Tomokazu,
Takahashi Tetsuya,
Nakamori Masahiro,
Yamazaki Yu,
Kurashige Takashi,
Nagano Yoshito,
Nishida Yoshihiko,
Izumi Yuishin,
Matsumoto Masayasu
Publication year - 2014
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12056
Subject(s) - lipid raft , biology , microbiology and biotechnology , neurofibrillary tangle , pathology , hippocampus , senile plaques , chemistry , alzheimer's disease , neuroscience , signal transduction , medicine , disease
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.