title: Granulovacuolar degenerations appear in relation to hippocampal phosphorylated tau accumulation in various neurodegenerative disorders.
abstract: BACKGROUND
  Granulovacuolar degeneration (GVD) is one of the pathological hallmarks of Alzheimer's disease (AD), and it is defined as electron-dense granules within double membrane-bound cytoplasmic vacuoles. Several lines of evidence have suggested that GVDs appear within hippocampal pyramidal neurons in AD when phosphorylated tau begins to aggregate into early-stage neurofibrillary tangles. The aim of this study is to investigate the association of GVDs with phosphorylated tau pathology to determine whether GVDs and phosphorylated tau coexist among different non-AD neurodegenerative disorders.
  
  
  METHODS
  An autopsied series of 28 patients with a variety of neurodegenerative disorders and 9 control patients were evaluated. Standard histological stains along with immunohistochemistry using protein markers for GVD and confocal microscopy were utilized.
  
  
  RESULTS
  The number of neurons with GVDs significantly increased with the level of phosphorylated tau accumulation in the hippocampal regions in non-AD neurodegenerative disorders. At the cellular level, diffuse staining for phosphorylated tau was detected in neurons with GVDs.
  
  
  CONCLUSIONS
  Our data suggest that GVDs appear in relation to hippocampal phosphorylated tau accumulation in various neurodegenerative disorders, while the presence of phosphorylated tau in GVD-harbouring neurons in non-AD neurodegenerative disorders was indistinguishable from age-related accumulation of phosphorylated tau. Although GVDs in non-AD neurodegenerative disorders have not been studied thoroughly, our results suggest that they are not incidental findings, but rather they appear in relation to phosphorylated tau accumulation, further highlighting the role of GVD in the process of phosphorylated tau accumulation.
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. yyamazak@hiroshima-u.ac.jp
authors.forename: Yuu
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Matsubara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurashige
authors.forename: Eisuke
authors.initials: E
authors.lastname: Dohi
authors.forename: Masanori
authors.initials: M
authors.lastname: Hiji
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Nagano
authors.forename: Takemori
authors.initials: T
authors.lastname: Yamawaki
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins
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