Alzheimer’s disease (AD) is the sixth leading cause of death in the U.S. Beyond the high economic and healthcare demands, it places a significant physical, emotional, and financial burden on family caregivers.

Patients with AD experience memory loss, confusion, mood and personality changes, and difficulty with language, often leading to social withdrawal. The biological cause of AD is linked to the accumulation of amyloid plaques, tau tangles, and synaptic loss in brain regions such as the hippocampus and cortex, which are critical for higher cognitive functions like memory retrieval.

Currently, there is no cure for Alzheimer’s, but treatments such as immunotherapy targeting amyloid plaques aim to help patients maintain their independence and quality of life for longer. Now, a potential addition to AD treatment has been synthesized by researchers at Scripps Research Institute in La Jolla, California. Their study, published in Antioxidants, highlights a stable form of carnosic acid (CA) — a compound naturally found in rosemary and sage — which decreases AD symptoms and could be well-suited for human trials.

Natural Compounds as Potential Drugs

Many modern drugs originate from medicinal herbs, which contain active compounds like alkaloids, glycosides, polyphenols, and terpenes. Well-known examples include morphine (from opium poppies), aspirin (from willow bark), and quinine (from cinchona trees).

A previous study by the research group demonstrated that carnosic acid can cross the blood-brain barrier and activate antioxidant and anti-inflammatory genes. This may explain rosemary’s theorized effect on memory, as inflammation is a key contributor to cognitive decline in AD.

Additionally, CA is a pro-electrophilic compound, meaning it activates only in response to inflammation, making it selectively active in areas of the brain affected by neuroinflammation. However, pure CA is highly unstable, rendering it unsuitable for clinical and commercial applications.

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Prodrug Shows Strong Performance

To overcome this obstacle, the researchers synthesized structurally related compounds and identified di-acetylated carnosic acid (diAcCA) as the most promising candidate due to its improved stability and bioavailability. This prodrug version of CA, which maintains a stable shelf life of over two years, was tested in genetically modified mice commonly used to study AD.

Behavioral tests assessing spatial learning and memory revealed that diAcCA significantly improved memory function and increased both the quality and quantity of synapses.

“We did multiple different tests of memory, and they were all improved with the drug,” said senior author Stuart Lipton, a clinical neurologist in La Jolla, California, in a press release. “And it didn’t just slow down the decline; it improved virtually back to normal.”

In addition to improving cognitive function, the compound successfully reduced inflammation and oxidative stress while also clearing proteins associated with amyloid plaques and tau tangles, which are biomarkers of Alzheimer’s disease.

Clinical Trials and Broader Applications

This modified version of CA holds significant potential for advancement into human clinical trials. Its safety profile, established through toxicity studies, and its selective activation mechanism suggest minimal side effects. When taken orally, diAcCA is fully converted to CA in the digestive tract and absorbed into the bloodstream, making it more bioavailable than CA itself.

The research team believes diAcCA could complement existing Alzheimer’s treatments by enhancing their effectiveness while mitigating side effects. Additionally, its anti-inflammatory properties may make it a viable candidate for treating other inflammation-related diseases, including type 2 diabetes, heart disease, and neurodegenerative disorders such as Parkinson’s disease.

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Having worked as a biomedical research assistant in labs across three countries, Jenny excels at translating complex scientific concepts – ranging from medical breakthroughs and pharmacological discoveries to the latest in nutrition – into engaging, accessible content. Her interests extend to topics such as human evolution, psychology, and quirky animal stories. When she’s not immersed in a popular science book, you’ll find her catching waves or cruising around Vancouver Island on her longboard.