Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice

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Journal of Neuroinflammation

tephanos Kyrkanides, Ross H Tallents, Jen-nie H Miller, Mallory E Olschowka, Renee Johnson, Meixiang Yang, John A Olschowka, Sabine M Brouxhon and M. KERRY O'Banion

Abstract (provisional)
Background
The purpose of this study was to investigate whether localized peripheral inflammation, such as osteoarthritis, contributes to neuroinflammation and neurodegenerative disease in vivo.

Method
S We employed the inducible Col1-IL1betaXAT 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 Abeta pathology, assessed by the number and size of amyloid plaques, in the APP/PS1; Col1-IL1betaXAT compound transgenic mouse.

Conclusion
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.

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