title: Cyclin-dependent kinase 5 immunoreactivity for granulovacuolar degeneration.
abstract: In addition to senile plaque and neurofibrillary tangles, granulovacuolar degeneration is a hallmark of Alzheimer's disease. A number of tau kinases, such as c-jun N-terminal kinase (JNK), glycogen-synthase kinase-3β (GSK3β), and casein kinase 1 (CK1), have been reported to be markers of granulovacuolar degeneration. In addition, cyclin-dependent kinase 5 (CDK5), which phosphorylates tau, has been shown to be abundantly expressed in neurofibrillary tangles in the hippocampus. CDK5 has a unique staining pattern, and therefore, has the potential to be a novel marker for granulovacuolar degeneration. In this study, we investigated the ability of CDK5 to be a marker for granulovacuolar degeneration using immunohistochemical analysis. Four Alzheimer's disease cases, three myotonic dystrophy (MyD) cases, and three control cases were subjected to immunohistochemistry and immunofluorescent techniques using anti-CDK5, anti-charged multivesicular body protein 2B (CHMP2B), anti-pSmad2/3, anti-ubiquitin (Ub), anti-phospho-TDP-43 and AT8 antibodies. Some CDK5-positive granules were morphologically similar to granulovacuolar degeneration intraluminal granules, and these granules overlapped with those immunopositive for pSmad2/3, Ub and phospho-TDP-43 established granulovacuolar degeneration markers. Moreover, CDK5-positive granulovacuolar degeneration and phosphorylated tau colocalized in pyramidal neurons in Alzheimer's disease and MyD cases. The numbers of CDK5-positive granules showed an inverse relationship with the degree of mature neurofibrillary tangles in each cell, as was the case with CHMP2B-positive granulovacuolar degeneration granules and neurofibrillary tangles. The presence of tau kinases including CDK5 in granulovacuolar degeneration might implicate that granulovacuolar degeneration is structurally involved in tau modification.
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakamori
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yuu
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurashige
authors.forename: Takemori
authors.initials: T
authors.lastname: Yamawaki
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009223:Myotonic Dystrophy / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051899:Smad2 Protein / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: C503812:CHMP2B protein, human; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D051899:Smad2 Protein; D025801:Ubiquitin; D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human