LA JOLLA, CA – For centuries, rosemary has been associated with memory, as referenced by Ophelia in Hamlet: “There’s rosemary, that’s for remembrance.” Now, researchers are exploring a key compound found in rosemary and sage carnosic acid for its potential to combat Alzheimer’s disease, the leading cause of dementia and the sixth leading cause of death in the U.S. Inflammation is a major contributor to the cognitive decline associated with the disease.

Carnosic acid is a powerful antioxidant and anti-inflammatory compound that activates the body's natural defense enzymes. However, its instability has limited its use as a drug. Scientists at Scripps Research have now developed a more stable form of carnosic acid, known as diAcCA. Once ingested, diAcCA is fully converted to carnosic acid in the gut, allowing it to be efficiently absorbed into the bloodstream.

Published in Antioxidants on February 28, 2025, the study demonstrated that treating mouse models of Alzheimer’s disease with diAcCA led to therapeutic levels of carnosic acid in the brain, resulting in enhanced memory and increased synaptic density indicating a higher number of nerve cell connections. Because synaptic loss is closely linked to cognitive decline in Alzheimer’s, this approach may help slow or even reverse disease progression.

Analysis of brain tissue revealed that the compound significantly reduced inflammation, a key driver of Alzheimer’s pathology. Notably, diAcCA is uniquely activated only in inflamed areas of the brain, minimizing potential side effects. Since carnosic acid is already on the FDA’s “generally regarded as safe” (GRAS) list, the researchers believe this could accelerate its path to clinical trials.

“By targeting inflammation and oxidative stress with diAcCA, we were able to increase synaptic connections in the brain,” said Dr. Stuart Lipton, MD, PhD, senior author and professor at Scripps Research. “We also saw a reduction in harmful phosphorylated-tau and amyloid-β, which are hallmarks of Alzheimer’s disease.”

Lipton’s previous research showed that carnosic acid crosses the blood-brain barrier and activates Nrf2, a pathway that triggers antioxidant and anti-inflammatory gene expression. However, the compound’s instability made it unsuitable as a drug due to rapid oxidation.

To overcome this, Lipton and Dr. Phil Baran, PhD, co-author and professor at Scripps Research, developed multiple derivatives of carnosic acid, ultimately selecting diAcCA for its stability, bioavailability, and drug-like properties. The team treated mice with diAcCA for three months, assessing their memory and spatial learning through behavioral tests, followed by microscopic brain tissue analysis.

“The results were striking,” said Lipton. “Not only did the treatment prevent cognitive decline, but it actually restored memory function close to normal levels.” Tissue analysis also revealed increased synaptic density and a significant reduction in phosphorylated-tau aggregates and amyloid-β plaques.

Importantly, diAcCA was well tolerated in mice, even reducing inflammation in the esophagus and stomach as it was metabolized into carnosic acid. Additionally, mice absorbed 20% more carnosic acid from diAcCA compared to pure carnosic acid, which often oxidizes before reaching the bloodstream.

Beyond its potential as a standalone Alzheimer’s treatment, Lipton suggests that diAcCA could enhance existing amyloid-targeting therapies by reducing side effects like brain swelling or bleeding (ARIA-E and ARIA-H).

With its strong safety profile, Lipton hopes diAcCA will advance quickly into clinical trials. He also sees broader applications beyond Alzheimer’s, including Parkinson’s disease, heart disease, type 2 diabetes, and other inflammatory conditions.

Source: https://www.scripps.edu/news-and-events/press-room/2025/20250319-lipton-alzheimers.html