Copper-based drug clears toxic Alzheimer's proteins and restores memory in mice

A new copper-ion compound developed by researchers at the Chinese Academy of Sciences cleared the amyloid-beta plaques and hyperphosphorylated tau proteins that mark Alzheimer's disease in mouse brains and restored memory performance close to that of healthy controls. The findings were published in the Journal of the American Chemical Society.

The team, led by Prof Wang Xin, designed a copper-peptide carrier able to cross the blood-brain barrier. The copper ion helps break the bonds between amyloid-beta fibrils; the same compound also reduces abnormal phosphorylation of tau proteins. After an eight-week course, mice scored about 92% of control performance on standard memory tests such as the Morris water maze.

Unlike conventional copper-chelation approaches, the team aimed not to remove copper from the brain but to balance it. Excess brain copper can be toxic, but trace copper is required for normal synaptic function. The new peptide carrier works by preserving copper homeostasis.

Alzheimer's disease is the most common cause of dementia worldwide, affecting roughly 55 million people. The US Food and Drug Administration approved the antibody therapies lecanemab in 2023 and donanemab in 2024, although debate continues about their efficacy and safety profiles. The new study points to a different chemical mechanism.

Earlier copper-related Alzheimer's work had focused on copper's possible role in driving disease. The new research suggests that copper, in the right molecular context, can also be used as a therapeutic tool. The compound's design routes copper toward amyloid aggregates without freeing it inside the brain.

Dr Bruce Miller, a neurologist at Berkeley who was not involved in the study, called the results "promising but still at the mouse level". Miller stressed that the gap between mouse and human brains matters and that clinical development will require at least two more years of safety and dose-finding work. He recalled that many non-antibody approaches have failed at the human trial stage.

The Wang team said it also analysed the compound's side-effect profile. Eight weeks of treatment showed no signs of liver or kidney toxicity, and copper accumulation remained within acceptable limits. The team noted that the long-term impact of copper buildup will require broader testing.

Current antibody drugs for Alzheimer's have drawbacks including intravenous administration, high cost and side effects such as brain swelling. A copper-ion compound offers the advantages of smaller molecular size and potential oral delivery. The Wang team said it is now working on an oral formulation.

Dr Susan Mitchell of the Alzheimer's Society described the work as "a diversification of the toolkit for the field". Mitchell said the past decade has been heavily focused on amyloid antibodies, but real progress will require parallel research into multiple mechanisms. She also highlighted the need for approaches targeting tau pathology.

The next steps are testing in small primate models followed by early-phase human trials. The Wang team said it has signed a licensing agreement with a Chinese biotech firm and could file a Phase 1 application by early 2027. Parallel filings in the US and EU are under review.