title: Distinct chronology of neuronal cell cycle re-entry and tau pathology in the 3xTg-AD mouse model and Alzheimer's disease patients.
abstract: Cell cycle re-entry in Alzheimer's disease (AD) has emerged as an important pathological mechanism in the progression of the disease. This appearance of cell cycle related proteins has been linked to tau pathology in AD, but the causal and temporal relationship between the two is not completely clear. In this study, we found that hyperphosphorylated retinoblastoma protein (ppRb), a key regulator for G1/S transition, is correlated with a late marker for hyperphosphorylation of tau but not with other early markers for tau alteration in the 3xTg-AD mouse model. However, in AD brains, ppRb can colocalize with both early and later markers for tau alterations, and can often be found singly in many degenerating neurons, indicating the distinct development of pathology between the 3xTg-AD mouse model and human AD patients. The conclusions of this study are two-fold. First, our findings clearly demonstrate the pathological link between the aberrant cell cycle re-entry and tau pathology. Second, the chronological pattern of cell cycle re-entry with tau pathology in the 3xTg-AD mouse is different compared to AD patients suggesting the distinct pathogenic mechanism between the animal AD model and human AD patients.
authors: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: Alex C
authors: AC
authors: Hradek
authors: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: Hyun-Pil
authors: HP
authors: Lee
authors: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: Sandra L
authors: SL
authors: Siedlak
authors: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: Sandy L
authors: SL
authors: Torres
authors: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: Wooyoung
authors: W
authors: Jung
authors: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: Ashley H
authors: AH
authors: Han
authors: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: Hyoung-gon
authors: HG
authors: Lee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D002453:Cell Cycle / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; C558298:Mapt protein, mouse; D016160:Retinoblastoma Protein; D016875:tau Proteins
keywords: Alzheimer's disease; animal model; cell cycle; retinoblastoma protein (Rb); tau; transgenic mouse