title: Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice.
abstract: BACKGROUND
  The purpose of this study was to investigate whether localized peripheral inflammation, such as osteoarthritis, contributes to neuroinflammation and neurodegenerative disease in vivo.
  
  
  METHODS
  We employed the inducible Col1-IL1βXAT mouse model of osteoarthritis, in which induction of osteoarthritis in the knees and temporomandibular joints resulted in astrocyte and microglial activation in the brain, accompanied by upregulation of inflammation-related gene expression. The biological significance of the link between peripheral and brain inflammation was explored in the APP/PS1 mouse model of Alzheimer's disease (AD) whereby osteoarthritis resulted in neuroinflammation as well as exacerbation and acceleration of AD pathology.
  
  
  RESULTS
  Induction of osteoarthritis exacerbated and accelerated the development of neuroinflammation, as assessed by glial cell activation and quantification of inflammation-related mRNAs, as well as Aβ pathology, assessed by the number and size of amyloid plaques, in the APP/PS1; Col1-IL1βXAT compound transgenic mouse.
  
  
  CONCLUSIONS
  This work supports a model by which peripheral inflammation triggers the development of neuroinflammation and subsequently the induction of AD pathology. Better understanding of the link between peripheral localized inflammation, whether in the form of osteoarthritis, atherosclerosis or other conditions, and brain inflammation, may prove critical to our understanding of the pathophysiology of disorders such as Alzheimer's, Parkinson's and other neurodegenerative diseases.
authors: Department of Children's Dentistry, Stony Brook University Health Science Center, Stony Brook, NY 11794, USA. Kyrkanides@gmail.com
authors: Stephanos
authors: S
authors: Kyrkanides
authors: Ross H
authors: RH
authors: Tallents
authors: Jen-Nie H
authors: JN
authors: Miller
authors: Mallory E
authors: ME
authors: Olschowka
authors: Renee
authors: R
authors: Johnson
authors: Meixiang
authors: M
authors: Yang
authors: John A
authors: JA
authors: Olschowka
authors: Sabine M
authors: SM
authors: Brouxhon
authors: M Kerry
authors: MK
authors: O'Banion
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D024042:Collagen Type I / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010003:Osteoarthritis / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D016229:Amyloid beta-Peptides; D024042:Collagen Type I; D053583:Interleukin-1beta; D011993:Recombinant Fusion Proteins