# Acceleration of Alzheimer’s Disease Pathology Due to Osteoarthritis-Associated Inflammation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $392,500

## Abstract

Project Summary/Abstract:
Alzheimer’s Disease (AD) and osteoarthritis (OA) are two of the most common health conditions affecting the
elderly population, and the economic and health impacts of AD and OA will markedly increase over the next
several decades as the elderly population grows. Deposition of beta-amyloid protein (Aβ) outside neurons and
abnormally phosphorylated Tau protein (pTau) inside neurons are two hallmark changes in the brain associated
with AD. Interestingly, our preliminary studies also found Aβ deposition and higher levels of pTau in the joints of
aged mice (96-weeks-old) and during OA progression in mouse knee joints following non-invasive ACL injury.
Additionally, we found that 17-month-old APP/PS1 mice, an established model of AD, had Aβ plaques in the
synovium of their knee joints. Taken together, these observations suggest a common underlying mechanism
between OA and AD, and raise the possibility that systemic inflammation associated with OA may accelerate
the progression of AD. The overall goal of our funded R01 grant is to determine how biomechanical interventions
can be utilized following joint injury to mitigate joint inflammation and affect the progression of post-traumatic
osteoarthritis (PTOA). The research proposed in this supplement will extend this line of investigation to determine
if systemic inflammation during OA progression accelerates AD progression in a genetic mouse model of AD
(APP/PS1 mice), and whether this effect can be mitigated by joint unloading during the early phase post-injury.
We hypothesize that OA and AD share a similar pathogenetic mechanism, and that inflammation associated with
OA progression can accelerate AD progression and cognitive decline. Our specific aim is to determine whether
OA-associated systemic inflammation accelerates the onset of AD progression and deterioration of cognitive
function in APP/PS1 mice, and whether this acceleration can be mitigated by early phase unloading. This
supplement extends the focus of our research to investigate the connection between OA and AD pathologies in
the joint and brain. This supplement study will lead to future R01 applications that will expand these results into
more comprehensive translational research on whether systemic inflammation from the peripheral organs such
as synovial joints may be associated with early-onset and faster progression of AD. It is also our long-term goal
to develop early diagnostic strategies and novel pharmaceutical interventions to prevent the accumulation of Aβ
and pTau in the joint and brain, which could potentially slow or prevent the progression of both OA and AD.

## Key facts

- **NIH application ID:** 10292125
- **Project number:** 3R01AR075013-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Blaine A. Christiansen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,500
- **Award type:** 3
- **Project period:** 2020-03-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10292125

## Citation

> US National Institutes of Health, RePORTER application 10292125, Acceleration of Alzheimer’s Disease Pathology Due to Osteoarthritis-Associated Inflammation (3R01AR075013-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10292125. Licensed CC0.

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