Alzheimer's: Rheumatoid Arthritis Drug Helps Reverse Tau-Related Symptoms

Could a drug previously used to treat rheumatoid arthritis be helpful in providing care for Alzheimer's patients?

The neurodegenerative illness that's estimated to affect over three million in the United States annually has no current cure. Yet scientists from the Gladstone Institute have discovered that the drug salsalate effectively reversed tau-related dysfuction in an animal model of frontotemporal dementia (FTD). The findings are published in the journal Nature Medicine.

The drug works by inhibiting tau acetylation, a chemical process that changes the function and properties in the brain, protecting it against cognitive impairments. When researchers tested the drug on a mouse model, they found that it successfully lowered tau levels in the brain, rescuing the organ from memory impairments and protecting against atrophy of the hippocampus--a region of the organ that's critical to memory formation.

Many tau-targeted drugs are available for patients with dementia, but it's not entirely clear just why the protein builds up in the brain, resulting in toxicity that contributes to the disease. Yet when researchers investigated post-mortem brains with Alzheimer's disease, the most common form of dementia, they found that tau acetylation was one of the first signs of pathology, even before tau tangles were detectable.

"Targeting tau acetylation could be a new therapeutic strategy against human tauopathies, like Alzheimer's disease and FTD," co-senior author Eric Verdin, MD, a senior investigator at the Gladstone Institutes, said in a news release. "Given that salsalate is a prescription drug with a long-history of a reasonable safety profile, we believe it can have immediate clinical implications."
In this recent study, researchers discovered that the drug could inhibit the enzyme p300 in the brain, which is elevated is elevated in Alzheimer's and triggers acetylation. Yet by blocking tau acetylation, tau turnover was enhanced, reducing tau levels in the brain and reducing memory deficits.

Future studies will help provide further information. Researchers have already initiated a clinical trial with the drug to help reduce tau levels in progressive supranuclear palsy, another tau-related medical condition.

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