Copper Regulation in the Brain Helps Prevent Memory Loss in Mice Suffering From Alzheimer’s

Chinese scientists have recently developed a molecule that allows the release of the copper trapped in amyloid plaques that is characteristic of Alzheimer’s disease. In mice, they have discovered that using TDMQ20, a Specific Copper Chelator helps reverse dementia.Alzheimer's Effects On The Brain

Alzheimer’s disease, which, affects millions of people worldwide, is the result of a slow degeneration of neurons. Starting in the hippocampus, a brain structure essential to our memory, it eventually spreads through the brain, leading to a loss of memory, bodily functions, and orientation in time and space, gradually limiting the autonomy and cognitive capacities of those affected.

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One of the characteristics of this neurodegenerative disease is the presence of amyloid plaques, extracellular accumulations of protein fragments, in particular Beta-amyloid.

Two researchers from the CNRS Coordination Chemistry Laboratory, together with scientists from Guangdong University of Technology and Shenzhen University, studied the copper present in the brain, especially in amyloid plaques, and its impact on brain degeneration in mice with Alzheimer’s. According to their results, published in the journal ACS Chemical Neuroscience, they were able to inhibit dementia with the help of a molecule that regulates the circulation of this nutrient in the brain.

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The role of copper in Alzheimer’s disease, a controversial issue

The role of copper in Alzheimer’s disease is a controversial issue that has been dividing the scientific community for several years: some believe that the accumulation of copper in blood vessels contributes to this degeneration of the brain, while others consider this nutrient to be preventive. Similarly, some studies show a copper deficiency in patients suffering from this disease and therefore the need to increase copper levels, while others point to a copper overload and therefore the need to reduce copper levels.

Metal ions such as copper but also zinc and iron are found in high concentrations in amyloid plaques in the brains of Alzheimer’s patients. In fact, these plaques absorb copper: they contain about five times more copper than a healthy brain. The researchers from the study have succeeded in developing TDMQ20 a patented molecule (Copper Chelator) that eases the flow of copper in the brains of mice by releasing the copper trapped in amyloid plaques. Once released, it is brought back into the brain, which, among other things, needs the copper to function.

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Promising results for the future

In the study, the researchers have administered the molecule orally to different groups of mouse models: two non-transgenic models mimicking the early stages of Alzheimer’s disease and a transgenic (genetically modified) model representing a more advanced stage of Alzheimer’s disease. In all three cases, the molecule reversed mice’ cognitive and behavioral decline due to neurodegeneration when administered over a 16-day period to improve the cognitive status and for three months to improve behavioral issues. The mice were tested constantly on different tasks to assess their memory and other cognitive functions. The mice were tested in different mazes and also underwent object recognition tests, the latter being particularly effective in assessing the development of declarative memory (the ability to consciously recall facts and events).

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This study could lead to advances in medicine for the treatment of neurodegenerative diseases like Alzheimer’s. The CNRS reports that they are looking for a pharmaceutical partner to develop preclinical trials with this drug candidate.

References

TDMQ20, a Specific Copper Chelator, Reduces Memory Impairments in Alzheimer’s Disease Mouse Models

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