Researchers at Monash University are sharing encouraging progress in the search for better ways to treat Alzheimer’s disease. In laboratory testing, a copper-based drug candidate called Cu(ATSM) helped reduce harmful protein buildup in the brain and supported stronger long-term spatial memory.

Published in ACS Chemical Neuroscience, the study points to a hopeful possibility: Cu(ATSM) may help restore an essential protective and cleaning role of the blood-brain barrier. By strengthening a natural waste-removal pathway, the compound could help guide future treatments for neurovascular dysfunction, an important contributor to Alzheimer’s disease.

A Brighter Path for Clearing Brain Waste

One of the major features of Alzheimer’s disease is the buildup of amyloid-beta, a toxic protein that can collect in the brain over time. In a healthy system, amyloid-beta is moved out of the brain and into the bloodstream through the blood-brain barrier.

This process depends in part on specialized transport proteins called P-glycoprotein, or P-gp, pumps. These pumps help clear unwanted material from the brain. In Alzheimer’s disease, however, they can lose effectiveness, making it harder for the brain to remove harmful waste.

The Monash team found that Cu(ATSM) helped improve this system in an Alzheimer’s model. Lead author Dr. Jae Pyun, from the Drug Delivery, Disposition and Dynamics theme at the Monash Institute of Pharmaceutical Sciences, said the treatment appeared to support healthier blood vessel function in the brain, reduce toxic proteins, and improve cognition.

"This is the first study to show that Cu(ATSM) can increase the abundance of P-gp clearance pumps in an Alzheimer's model, by 24.1 percent, effectively linking the repair of the blood-brain barrier to a reduction in toxic proteins and improved cognitive function," Dr. Pyun said.

"By improving the pumps, the brain can finally clear out the trapped waste. Over 56 days, the treatment reduced toxic amyloid-beta by 42 percent and improved spatial learning by nearly 44 percent."

Encouraging Potential From an Existing Drug Candidate

Another positive feature of Cu(ATSM) is that it is not entirely new to medical research. Because it has already been tested for safety in other neurological conditions, researchers believe it may have a clearer path toward future human studies.

Senior author Professor Joseph Nicolazzo, Director of the Centre for Drug Candidate Optimisation at MIPS, said the compound has qualities that make it especially promising.

"Cu(ATSM) is a copper compound with anti-inflammatory and neuroprotective properties that has already progressed to clinical testing for conditions like Parkinson's and ALS," Professor Nicolazzo said.

"Because reducing amyloid burden is clinically proven to improve functional outcomes, these preclinical results strongly support the rationale for testing this drug in early symptomatic Alzheimer's disease."

Understanding How the Brain Removes Harmful Proteins

While the results are uplifting, researchers are continuing to explore exactly how amyloid-beta exits the brain once the blood-brain barrier’s clearing function is improved.

The team thinks Cu(ATSM) may do more than increase P-gp pump activity. It may also help microglia, the brain’s immune cells, work more effectively as they consume and break down toxic amyloid plaques.

Future studies will look more closely at the biological routes that allow these proteins to move from the brain into the bloodstream. The findings add meaningful support for continued research into biometal-based therapies such as Cu(ATSM), especially for Alzheimer’s-related blood vessel dysfunction and memory decline.

Hope Amid a Growing Health Challenge

Alzheimer’s disease and other dementias remain a serious global health concern. In Australia, dementia has recently overtaken coronary heart disease as the leading cause of death.

As populations age and dementia-related deaths increase, the need for treatments that can slow or prevent cognitive decline is becoming more urgent. This new Monash-led research offers a hopeful step forward and adds momentum to the search for therapies that may protect memory and brain health.

The study was led by Dr. Jae Pyun and included co-authors Pranav Runwal, Oliver Fuller, Casey Egan, Professor Mark Febbraio, Associate Professor Jennifer Short and Professor Joseph Nicolazzo from the Monash Institute of Pharmaceutical Sciences, along with Dr. Asif Noor, Celeste Mawal, Professor Paul Donnelly, and Professor Ashley Bush from the University of Melbourne.