Brain and knee joint degeneration following anterior cruciate ligament injury in a mouse model of Alzheimer’s disease

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Abstract
Alzheimer’s disease (AD) and osteoarthritis (OA) are 2 of the most common health conditions affecting the elderly. Recent studies in mice and humans have described an association between OA and AD, with prevalent OA increasing the risk of developing AD-like cognitive declines. In this study, we investigated brain and knee joint degeneration and neurocognitive dysfunction in a mouse model of AD (APP/PS1 double transgenic mice) in the presence or absence of OA induced by non-invasive ACL rupture. We hypothesized that OA would be associated with increased beta amyloid (Aβ) and phosphorylated tau (pTau) in the injured joint and brain and would be associated with accelerated cognitive decline in APP/PS1-Tg mice. Non-invasive knee injury was performed at 7 mo of age in male and female APP/PS1-Tg mice and non-transgenic (WT) littermates. Neurocognitive tests, including open field, novel object recognition, and Morris water maze, were performed 6 wk post-injury. Knees were also assessed at 6 wk post-injury to quantify OA, and Aβ, Tau, and pTau levels in the brain and knee joints. We found that female APP/PS1-OA mice had significantly more osteophyte formation than WT-OA mice, and significantly greater Aβ and pTau levels in the brain and knee joints than in WT or APP/PS1-Sham mice. These results provide insights about the pathoetiology of AD and OA and suggest possible common mechanisms connecting OA-associated inflammation to cognitive function. Identifying novel mechanisms of crosstalk between these 2 conditions could improve clinical care and quality of life for at-risk patient populations.
Funding Information
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR075013-02S1)
  • National Institutes of Health (R01 AR075013-02S1)

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