title: The role of neuroinflammation and amyloid in cognitive impairment in an APP/PS1 transgenic mouse model of Alzheimer's disease.
abstract: OBJECTIVE
  Both amyloid deposition and neuroinflammation appear in the early course of Alzheimer's disease (AD). However, the progression of neuroinflammation and its relationship with amyloid deposition and behavioral changes have not been fully elucidated. A better understanding the role of neuroinflammation in AD might extend our current knowledge to therapeutic intervention possibilities.
  
  
  METHODS
  This study systematically characterized changes in behavioral abnormalities in APP/PS1 transgenic mice. Brain pathology measures were performed in post-mortem brain tissues of mice from 2 to 22 months.
  
  
  RESULTS
  APP/PS1 mice exhibited significant memory deficits from 5 months old, which were aggravated at the later stage of life. However, the degree of memory impairments reached a plateau at 12 months. An early appearance of amyloid plaques was at 3 months with a linear increase throughout the disease course. CD11b-positive microglia and glial fibrillary acidic protein-(GFAP) positive astrocytes were first detected at 3 months with a close association with amyloid plaques. Yet, the rate of changes in glial activation slowed down from 12 months despite the steady increase in Aβ.
  
  
  CONCLUSIONS
  These findings provided evidence that neuroinflammation might be involved in the development and progression of cognitive deficits in APP/PS1 mice, suggesting novel intervention and prevention strategies for AD.
authors.affiliation: Department of Pharmacology and Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.|Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, MB, Canada.
authors.forename: Shenghua
authors.identifier: http://orcid.org/0000-0002-2238-4960
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
authors.forename: Junhui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: First Affiliated Hospital, Henan University, Kaifeng, Henan, China.
authors.forename: Jue
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Pharmacology and Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Jiming
authors.initials: J
authors.lastname: Kong
authors.affiliation: Department of Pharmacology and Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.|Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, MB, Canada.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: Alzheimer's disease; astrocyte; microglia; neuroinflammation