The herb rosemary has long been associated with memory, famously referenced by Ophelia in Shakespeare’s Hamlet: “There’s rosemary, that’s for remembrance.” Now, researchers are investigating carnosic acid, a natural compound found in both rosemary and sage, for its potential role in Alzheimer’s disease—the leading cause of dementia and the sixth leading cause of death in the U.S.

Carnosic acid is known for its antioxidant and anti-inflammatory properties, activating enzymes that support the body’s natural defense system. However, due to its instability, it is unsuitable as a drug. Scientists at Scripps Research have now developed diAcCA, a stable derivative that converts into carnosic acid in the gut before being absorbed into the bloodstream.

A study published in Antioxidants, demonstrated that treating Alzheimer’s mouse models with diAcCA led to higher therapeutic levels of carnosic acid in the brain, improving memory and synaptic density—a key indicator of cognitive function. Given that the loss of neuronal synapses is closely linked to Alzheimer’s progression, this approach could help slow or even reverse cognitive decline.

Moreover, brain tissue analysis revealed that diAcCA significantly reduced inflammation, working selectively in affected brain regions while minimizing side effects. Since carnosic acid is on the FDA’s "Generally Regarded as Safe" (GRAS) list, diAcCA has the potential for a fast-tracked clinical trial process.

Senior researcher Dr. Stuart Lipton, a neurologist at Scripps Research, highlighted the compound’s ability to not only reduce brain inflammation and oxidative stress but also decrease the accumulation of phosphorylated-tau and amyloid-β plaques—key hallmarks of Alzheimer’s.

Previously, Lipton’s team confirmed that carnosic acid can cross the blood-brain barrier and activate the Nrf2 transcriptional pathway, turning on genes that reduce oxidative stress. However, its instability and rapid oxidation limited its drug potential. By synthesizing diAcCA, Lipton and co-author Dr. Phil Baran developed a more stable, bioavailable version with promising therapeutic effects.

During a three-month treatment period, mice receiving diAcCA showed significant memory improvements in behavioral tests, with their cognitive function nearly restored to normal. Additionally, tissue analysis revealed higher synaptic density and reduced amyloid and tau aggregates. The compound was well tolerated, with additional benefits for gut health, as it reduced baseline inflammation in the esophagus and stomach.

Another key finding was that diAcCA increased carnosic acid absorption by 20%, compared to direct carnosic acid intake, due to reduced oxidation during storage and digestion.

Dr. Lipton envisions diAcCA as a standalone therapy or a complementary treatment alongside existing amyloid antibody drugs to enhance their effectiveness and reduce side effects like ARIA-E and ARIA-H, which involve brain swelling and bleeding.

Beyond Alzheimer’s, Lipton believes diAcCA could have broader applications for other inflammation-related conditions, including type 2 diabetes, heart disease, and neurodegenerative disorders like Parkinson’s disease. With its promising safety profile, the compound may soon advance to clinical trials, offering new hope in the fight against Alzheimer’s and related diseases. 

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