title: Amyloid β Protein Aggravates Neuronal Senescence and Cognitive Deficits in 5XFAD Mouse Model of Alzheimer's Disease.
abstract: BACKGROUND
  Amyloid β (Aβ) has been established as a key factor for the pathological changes in the brains of patients with Alzheimer's disease (AD), and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in the AD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type (WT) mice to determine whether senescent neurons are present in the transgenic AD mouse model.
  
  
  METHODS
  The 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes (DEGs) were screened by quantitative real-time polymerase chain reaction. Cognitive performance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ (oAβ) (1-42) was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence.
  
  
  RESULTS
  In 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes (labeled as glutamine synthetase), nil expression in activated microglia (labeled as Iba1), and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ (1-42) induced the production of senescence-related protein p16, but not p53 in vitro, which was in line with the in vivo manifestation.
  
  
  CONCLUSIONS
  oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for AD population.
authors.affiliation: Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Chen
authors.affiliation: Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Pan
authors.affiliation: Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Xiao-Man
authors.initials: XM
authors.lastname: Dai
authors.affiliation: Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Cui
authors.affiliation: Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Wu
authors.affiliation: Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Yuan-Gui
authors.initials: YG
authors.lastname: Zhu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases