Knee osteoarthritis accelerates amyloid beta deposition and neurodegeneration in a mouse model of Alzheimer’s disease

Abstract

Knee osteoarthritis (OA) is characterized by knee cartilage degeneration and secondary bone hyperplasia, resulting in pain, stiffness, and gait disturbance. The relationship between knee OA and neurodegenerative diseases is still unclear. This study used an Alzheimer’s disease (AD) mouse model to observe whether osteoarthritis accelerates dementia progression by analyzing brain histology and neuroinflammation. Knee OA was induced by destabilizing the medial meniscus (DMM) in control (WT) and AD (5xFAD) mice before pathological symptoms. Mouse knee joints were scanned with a micro-CT scanner. A sham operation was used as control. Motor and cognitive abilities were tested after OA induction. Neurodegeneration, β-amyloid plaque formation, and neuroinflammation were analyzed by immunostaining, Western blotting, and RT-PCR in brain tissues. Compared with sham controls, OA in AD mice increased inflammatory cytokine levels in brain tissues. Furthermore, OA significantly increased β-amyloid deposition and neuronal loss in AD mice compared to sham controls. In conclusion, knee OA accelerated amyloid plaque deposition and neurodegeneration in AD-OA mice, suggesting that OA is a risk factor for AD.

WITHDRAWN: Associations of cognitive decline, peripheral inflammatory factors and hippocampal subregions volume in knee osteoarthritis - a longitudinal MRI study

“…Previous studies (Innes & Sambamoorthi, 2018; Lin et al, 2022) showed that patients with KOA have impaired cognitive function, mainly in memory disturbances which are partly consistent with our results. Gupta et al (Gupta et al, 2023) found that OA was a risk factor for Alzheimer's disease (AD)…”

Molecular Mechanisms Linking Osteoarthritis and Alzheimer’s Disease: Shared Pathways, Mechanisms and Breakthrough Prospects

“…In a lead study conducted by Gupta et al [ 102 ] to analyze the association between knee OA and AD on 5xFAD transgenic mice models, induction of OA in the AD mice led to a more exacerbated symptom in certain brain regions, increased inflammation including elevated IL-1β and TNF levels, and more Aβ disposition. This study helps us understand how OA development can exacerbate pathologies related to AD development.…”

The Functions and Phenotypes of Microglia in Alzheimer’s Disease

“…During these chronic pain states, microglia release pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, which cause dysfunction in synaptic remodeling and brain connectivity [ 100 , 113 , 116 ]. In addition, it has been reported to increase the mRNA expression of IL-1β and TNF-α and accelerate Aβ deposition in 5xFAD model mice [ 117 ]. Chronic pain-induced microglial inflammation is associated with AD progression.…”