New Copper-Based Medication Eliminates Alzheimer's Toxins and Improves Memory
- 6 days ago
- 4 min read
An experimental copper-based drug has nearly halved toxic proteins associated with Alzheimer's disease and significantly improved memory in animals. This discovery could pave the way for a new generation of treatments focused on naturally cleaning the brain.
Alzheimer's disease is the most common form of dementia and affects millions of people worldwide. One of the main characteristics of the disease is the accumulation of beta-amyloid proteins in the brain. These proteins can form toxic plaques that impair communication between neurons, promote inflammation, and contribute to the progressive loss of memory and other cognitive functions.
Although several treatments are being developed to combat these plaques, scientists continue to seek more effective strategies to help the brain eliminate these harmful substances.
One of the brain's natural forms of protection involves the blood-brain barrier, a highly specialized structure that controls what enters and leaves brain tissue.
Within this barrier, there is a protein called P-glycoprotein, which acts as a kind of "cleaning pump," helping to remove potentially harmful substances, including some of the beta-amyloid protein. Previous studies have shown that this protein tends to function worse in Alzheimer's disease, hindering the elimination of brain toxins.
In this study, researchers investigated an experimental compound called copper diacetyl bis(4-methyl-3-thiosemicarbazone), known as Cu(ATSM). This drug has the ability to cross the blood-brain barrier and transport copper to specific regions of the brain. Copper is an essential mineral for various biological functions, including the activity of proteins involved in the protection and maintenance of neurons.
To test the treatment's effectiveness, scientists used genetically modified mice to develop characteristics similar to those observed in human familial Alzheimer's disease. These animals accumulate large amounts of beta-amyloid in their brains and exhibit memory deficits as they age. The mice received the medication daily for 56 days, while another group received only a substance with no therapeutic effect to serve as a comparison.
At the end of the treatment, the researchers analyzed the animals' brains using various laboratory techniques. They measured copper levels, assessed the amount of P-glycoprotein in cerebral blood vessels, and determined the amount of beta-amyloid accumulated in the cerebral cortex, a region important for memory and cognition. In addition, they conducted behavioral tests to evaluate the animals' learning capacity and spatial memory.
The results were quite encouraging. The treatment restored P-glycoprotein levels in cerebral blood vessels and significantly increased copper concentrations in these structures. As a consequence, there was an approximately 42% reduction in the levels of the most toxic form of beta-amyloid protein found in the brains of the animals.
The researchers also observed a trend toward improvement in the brain's ability to eliminate these harmful proteins, suggesting that the drug may help the brain's natural cleaning mechanisms function more efficiently.
The most impressive finding was observed in memory tests. Treated mice showed an almost 44% improvement in learning and long-term spatial memory compared to untreated animals. In other words, in addition to reducing the load of toxic proteins in the brain, the drug also produced functional benefits that could be observed in the animals' behavior.
Despite the promising results, it is important to highlight that this study was conducted exclusively on mice. This means that we do not yet know if the same benefits will occur in humans. Many treatments that work in animal models do not show the same results in clinical trials. However, Cu(ATSM) has an important advantage: it has already been studied in other neurodegenerative diseases, and its ability to reach the brain has already been demonstrated in previous research.
The authors conclude that Cu(ATSM) may represent a new therapeutic approach for Alzheimer's by acting simultaneously on cerebral blood vessels, beta-amyloid elimination mechanisms, and cognitive function.
Although clinical studies are needed to confirm its efficacy and safety in humans, the results suggest that restoring the brain's natural cleaning systems may be a promising strategy to slow the progression of the disease.
Lead author Dr. Jae Pyun (left) and senior author Professor Joseph Nicolazzo (right). Credit: Monash University.
LEIA MAIS:
Cu(ATSM) Restores Blood–Brain Barrier Abundance of P-Glycoprotein and Improves Cognitive Function in the APP/PS1 Mouse Model of Alzheimer’s Disease
Jae Pyun, Asif Noor, Pranav Runwal, Celeste Mawal, Oliver K. Fuller, Casey L. Egan, Mark A. Febbraio, Paul S. Donnelly, Jennifer L. Short, Ashley I. Bush, and Joseph A. Nicolazzo
ACS Chem. Neurosci. 2026, 17, 12, 2389–2405
Abstract:
Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) peptides in the brain. P-glycoprotein (P-gp), a key efflux transporter at the blood–brain barrier (BBB), plays a crucial role in the clearance of Aβ. Using the APP/PS1 mouse model of familial AD, this study investigated the effect of copper diacetyl bis(4-methyl-3-thiosemicarbazone) (Cu(ATSM)) on brain microvascular abundance and function of P-gp and the associated effects on exogenous Aβ clearance, brain amyloid burden, and cognitive function. Compared to vehicle-treated 10 month-old APP/PS1 mice, Cu(ATSM) (30 mg/kg/day for 56 days) restored brain microvascular P-gp abundance (24.1%) and Cu concentrations (229.8%) as well as significantly reduced brain cortical concentrations of human Aβ42 (hAβ42) (42.1%) in APP/PS1 mice. Cu(ATSM) treatment led to a trend toward improved brain clearance (11.9%) of 125I-Aβ42 that was cortically injected into APP/PS1 mice compared to vehicle-treated APP/PS1 mice. Importantly, Cu(ATSM) treatment led to significantly improved (43.8% p = 0.0087) learning and long-term spatial memory in APP/PS1 mice, assessed by the Barnes maze paradigm. Inductively coupled plasma mass spectrometric analysis revealed increased Cu concentrations in brain microvessel-enriched fractions. In APP/PS1 mice, Cu(ATSM) restored brain microvascular P-gp abundance, which was associated with lowered cortical hAβ42, and improved long-term spatial memory, indicating neurovascular target engagement accompanied by amyloid lowering and behavioral benefit. Together with established BBB penetration and ongoing safety and tolerability evaluation in neurodegenerative populations, these findings propose Cu(ATSM) as a potential therapeutic application of biometal modulation targeting neurovascular dysfunction and Aβ burden in AD.
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