Rheumatoid arthritis signaling protein reverses Alzheimer’s disease in mouse model

Tampa, FL (August 23, 2010) — A signaling protein released during rheumatoid arthritis dramatically reduced Alzheimer’s disease pathology and reversed the memory impairment of mice bred to develop symptoms of the neurodegenerative disease, a new study by the University of South Florida reports. Researchers found that the protein, GM-CSF, likely stimulates the body’s natural scavenger cells to attack and remove Alzheimer’s amyloid deposits in the brain.

The study appears online today in the Journal of Alzheimer’s Disease.

People with rheumatoid arthritis, a chronic disease leading to inflammation of joints and surrounding tissue, are less likely than those without arthritis to develop Alzheimer’s. While it was commonly assumed that non-steroidal anti-inflammatory drugs may help prevent onset and progression of Alzheimer’s disease, recent NSAID clinical trials proved unsuccessful for patients with Alzheimer’s.

The USF researchers are among the first to look at what effect innate immunity gone awry in rheumatoid arthritis may play in protecting against Alzheimer’s disease.

“Our findings provide a compelling explanation for why rheumatoid arthritis is a negative risk factor for Alzheimer’s disease,” said principal investigator Huntington Potter, PhD, professor of molecular medicine at the USF Health Byrd Alzheimer’s Institute and director of the Florida Alzheimer’s Disease Research Center.

“Moreover, the recombinant human form of GM-CSF (Leukine®) is already approved by the FDA and has been used for years to treat certain cancer patients who need to generate more immune cells,” Dr. Potter said. “Our study, along with the drug’s track record for safety, suggests Leukine should be tested in humans as a potential treatment for Alzheimer’s disease.”

The researchers analyzed three rheumatoid arthritis growth factors in mouse models and identified the signaling protein GM-CSF as the most promising for potential protective benefit against Alzheimer’s disease. Then, they peripherally injected GM-CSF into two groups of mice — those genetically altered to develop memory problems mimicking Alzheimer’s disease and normal, aged mice. Behavioral tests confirmed the Alzheimer’s mice were exhibiting signs of memory impairment at age 12 months. Another two control groups of mice — the Alzheimer’s mice and normal mice — were administered saline (placebo).

After the 10th day of injections, all the mice began a series of behavioral testing. At the end of the 20-day study, the cognitively impaired mice treated with GM-CSF performed substantially better on tests measuring their working memory and learning. In fact, their memories were similar to normal aged mice without dementia. Even the normal mice treated with GM-CSF performed slightly better than their untreated peers. The Alzheimer’s mice administered saline continued to do poorly on the tests.

“We were pretty amazed that the treatment completely reversed cognitive impairment in 20 days,” said Tim Boyd, PhD, who, together with Steven Bennett, PhD, is a study lead author.

In addition, the brains of GM-CSF-treated Alzheimer’s mice showed more than a 50-percent decrease in beta amyloid, a substance forming the sticky clumps of plaques that are a hallmark of Alzheimer’s disease. This reduction in Alzheimer’s plaques and associated restoration of memory was accompanied by more immune cells known as microglia in the brain. Microglia are like the body’s natural garbage collection cells that rush to damaged or inflamed areas to get rid of toxic substances.

The researchers suggest that GM-CSF boosted during the immune system overdrive of rheumatoid arthritis helps harness the beneficial properties of inflammation in the brain. The protein may do this by recruiting more microglia from the peripheral blood into the brain to remove Alzheimer’s plaques, Dr. Potter said. An apparent increase in neural cell connections in the brains of the GM-CSF-treated mice may also help explain GM-CSF’s association with improving memory decline in Alzheimer’s disease, the researchers said.

The USF Health Byrd Alzheimer’s Institute plans to begin a pilot clinical trial later this year investigating GM-CSF (Leukine) in patients with mild or moderate Alzheimer’s disease.

Journal article (online):
“GM-CSF up-regulated in Rheumatoid Arthritis reverses cognitive impairment and amyloidosis in Alzheimer mice;” Tim D. Boyd, PhD; Steven P. Bennett, PhD; Takashi Mori, DVM, PhD; Nikolas Governatori, BS; Melissa Runfeldt, BS; Michelle Norden; Jaya Padmanabhan, PhD; Peter Neame, PhD; Inge Wefes, PhD; Juan Sanchez-Ramos, PhD, MD; Gary W. Arendash, PhD, Huntington Potter, PhD; Journal of Alzheimer’s Disease; Vol. 21:2 (August 23, 2010).

About USF Health

USF Health (www.health.usf.edu) is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $380.4 million in research grants and contracts last year, the University of South Florida is one of the nation’s top 63 public research universities and one of only 25 public research universities nationwide with very high research activity that is designated as community-engaged by the Carnegie Foundation for the Advancement of Teaching.

About the Journal of Alzheimer’s Disease

The Journal of Alzheimer’s Disease (http://www.j-alz.com) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer’s disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer’s Disease has an Impact Factor of 3.83 according to Thomson Reuters’ Journal Citation Reports (2010). The Journal is published by IOS Press (http://www.iospress.nl).



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3 thoughts on “Rheumatoid arthritis signaling protein reverses Alzheimer’s disease in mouse model”

  1. Thanks for the article. It is very informative. Even I was not aware that there is some connection between both the diseases and a rheumatoid arthritis sufferer need not worry about Alzheimer’s,

  2. Thank you for sharing. I had no idea that there was a relation between the two diseases. One of my closest friends has RA, and it is so sad to see, especially at such a young age. My Grandmother also had Alzheimer’s a few years back before she passed away. It is a terrible disease that truly hurts the entire family.

    I also work with senior citizens every day, helping them cover the out of pocket gaps brought on by government Medicare. Many of my clients have varying degrees of Alzheimer’s and arthritis. It is good to know that its likely one person won’t suffer from both. I will definitely pass this information along. Thank you!

  3. As a rheumatoid arthritis sufferer it’s very reassuring to know that I’m much less likely to have to deal with Alzheimer’s too in the future. Thank you for this compelling post. Jane C

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