Could an arthritis drug also help treat Alzheimer's disease?

"Arthritis drug could soon reverse Alzheimer's symptoms after successful tests on mice," The Independent reports. The drug – salsalate – may help regulate levels of the abnormal tau protein associated with Alzheimer's disease, which could improve memory skills.

Salsalate, which belongs to the non-steroidal anti-inflammatory drug (NSAIDs) class of medicines, has been used for many years. And as The Daily Telegraph points out, it was even mentioned by the 5th century BC physician Hippocrates.

This study was conducted in mice with clumps of tau in their brains. Salsalate was given to the mice and was found to block the process that can lead to a further protein build up. Treated mice also performed better in tests designed to assess memory skills.

While these findings show promise, the studies were conducted in mice and were only conducted for a couple of months. 

Further human studies will be required to determine how effective the drug is and over what timescale. But because this drug has already been approved for use in humans, these tests may come sooner rather than later.

To reduce your risk of Alzheimer's disease, a healthy and active lifestyle is recommended. This includes stopping smoking, reducing your alcohol consumption, having a good diet and taking regular exercise. 

Where did the story come from?

The study was carried out by researchers from several Gladstone Institutes in San Francisco, the University of California, Stanford University School of Medicine, and the Buck Institute for Research on Aging.

Funding was provided by Tau Consortium and the US National Institutes of Health.

The study was published in the peer-reviewed journal Nature Medicine.

This story has been reported in a number of media sources, but it is misleading to say the drug could "soon reverse Alzheimer's," as The Independent put it. These findings were in mice, and trials also need to be conducted in humans. 

The Daily Telegraph correctly informed readers that, "While there is potential that drugs used to treat other diseases could be of benefit in dementia, nobody should be taking such drugs until clinical trials have shown them to be safe and effective for the treatment of dementia."

Salsalate can be dangerous for certain groups of people, such as those recovering from heart surgery. You should never take salsalate unless it's been prescribed for you by a qualified doctor.  

What kind of research was this?

This animal study in mice investigated the changes occurring in the brain in a mice model of the early stages of Alzheimer's disease.

This condition is characterised by the accumulation of tau proteins and a reduction in brain volume, especially in an area called the hippocampus, which is important for forming memory. 

Further investigation was carried out to assess the effect of the prescription drug, salsalate, on the accumulation of tau proteins and brain volume.

While this is a good method to investigate effects, any findings would have to be confirmed in humans.  

What did the research involve?

Researchers used human brain samples to investigate how the tau protein builds up in the brain in Alzheimer's disease.

They identified how greater levels of tau acetylation – a chemical process that alters the tau protein, causing it to build up and induce cognitive defects – was associated with progression of disease.

The study then involved laboratory mice with dementia to firstly confirm a similar mechanism of tau acetylation and disease, and then test the effect of salsalate on disease progression.

Mice with dementia and normal mice were assigned to receive salsalate or a placebo daily. Female mice aged eight to nine months were treated for a total of 60 days, and male mice aged seven to eight months were treated for 84 days. Brain volume was assessed at the end of the trial.

Behavioural tests for spatial learning and memory retention were conducted on the 35th day for female mice and about the 60th day for the male mice. Investigators who performed the dosing and behavioural tests were blinded to the type of mice or treatment received to reduce the risk of bias.  

What were the basic results?

The study identified a chemical change called tau acetylation as an early change in Alzheimer's disease brains in mice. The altered tau protein is slow to break down, causing an accumulation and leading to cognitive decline.

Researchers found salsalate prevented the chemical change occurring, allowing the tau protein to break down as normal and reducing its build up.

At eight months, the brain volume in the hippocampus was the same in both groups of female mice. After treatment at 10 months of age, the volume had reduced in mice with dementia that had been given a placebo. 

In mice with dementia given salsalate, there was no reduction in brain volume compared with normal mice, showing it had halted this part of the disease process. Similar results were found for the male mice.  

How did the researchers interpret the results?

The researchers concluded salsalate lowers levels of tau protein with protective effects.

Targeting tau acetylation could be a new therapeutic strategy against neurodegenerative disease, they say. 

Conclusion

Salsalate was found to inhibit the tau acetylation process and prevent an accumulation of the tau protein in the brains of mice. It was also found to improve memory retention and prevent the loss of hippocampal brain volume.

However, we do not know whether salsalate would replicate the effects observed in mice when used in humans. But these findings do provide a route for further research in a drug already prescribed to people with arthritis. 

Although we are aware of the potential side effects at doses suitable to help arthritis, we don't know what dose may be required to be effective against dementia. This could alter the side effect profile if the dosage needs to be higher.

It is unclear whether this drug is actually prescribed in the UK, as it is unlicensed for use in this country. Salsalate is also currently being used in a clinical trial for another brain disease. 

Other ways to reduce your risk of Alzheimer's disease include stopping smoking, lowering your alcohol intake, eating a good diet and taking regular exercise.