An existing prescription drug may be able to help in the fight against Alzheimer's, according to research published in Nature Medicine.
A study at the Gladstone Institutes in San Francisco, CA, has found that salsalate, already established as a treatment for rheumatoid arthritis, is able to prevent the accumulation of the protein tau - known to cause toxicity and contribute to cognitive degeneration. The discovery has implications for frontotemporal dementia (FTD) and Alzheimer's disease.
Tau acetylation is a chemical process that can change the function and properties of a protein. It leads to neurodegeneration and cognitive deficits.
Acetylated tau is a highly toxic form of the protein. The acetylation process is triggered by the enzyme p300, raised levels of which are found in patients with Alzheimer's.
Scientists have known for some time that tau is a factor in dementia, but how it builds up and contributes has eluded researchers, and no drugs have been developed to target it as yet. The Gladstone team hopes to have made a step forward.
The team, including Li Gan, PhD, senior co-author and associate investigator at Gladstone, studied postmortem brains to learn more about tau accumulation. They found that tau accumulates in the brain early in the development of Alzheimer's, from where it leads to further tau accumulation and toxicity, causing further dysfunction.
Tests on mice showed that when tau is acetylated, the ability of neurons to degrade it is reduced, causing further build-up in the brain, leading to atrophy and further cognitive impairment. Memory tests on the mice supported this finding.
Salsalate reverses tau-induced memory deficits, brain cell loss
In the mouse model, the scientists found that by using salsalate, they were able to reverse tau-related dysfunction, including impairments similar to those in Alzheimer's.
Salsalate inhibits the enzyme p300, so that it blocks tau acetylation, enhancing tau turnover and reducing tau levels in the brain.
In this way, it effectively reverses tau-induced memory deficits and prevents loss of brain cells. It also protects against atrophy of the hippocampus, a region essential for memory formation, which is impacted by dementia.
Salsalate even appears to be effective after the disease has set in, achieving not only delay of symptoms but also rescue and repair.
Gan says that the scientists have identified an approach that "reverses all aspects of tau toxicity." She notes that even though salsalate was given after the onset of disease, "profound protective effects" were achieved, suggesting that salsalate may offer an effective mode of treatment against dementia and Alzheimer's.
As co-senior author Dr. Eric Verdin, a senior investigator at Gladstone, says:
"Targeting tau acetylation could be a new therapeutic strategy against human tauopathies, like Alzheimer's disease and FTD. Given that salsalate is a prescription drug with a long history of a reasonable safety profile, we believe it can have immediate clinical implications."
Recently, Medical News Today reported on research suggesting stress can contribute to Alzheimer's.