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Researchers Discover How Alzheimer's Disease Kills Brain Cells

Kathleen Blanchard's picture

Until now, scientists have been uncertain exactly how Alzheimer’s disease kills brain cells, causing debate among researchers. The results of a new study show how amyloid plaques, found in the brain of Alzheimer’s patients, cause brain cells to die.

Researchers from University of Michigan and the University of California, San Diego were able to observe spikes in electrical currents across artificial cell membranes and in the membranes of live human cancer cells in the presence of the amyloid-beta peptide. What that told the scientists is that amyloid peptides poke holes in the cell membranes, allowing influx of calcium. Prior to the current research, it was believed that amyloid peptides thinned the cell membranes, producing calcium ion fluctuations. When ions become imbalanced, cell death results.

The researchers say that controversy about how Alzheimer’s disease kills brain cells has been a hindrance to developing new drugs. Michael Mayer, an assistant professor in the U-M departments of Biomedical Engineering and Chemical Engineering says, “It is our hope that putting this disagreement to rest by showing that amyloid beta peptides do not thin membranes but instead form discrete pores in membrane can help the field move forward at a more rapid pace."

Mayer explains how his team was able to produce thinning of cell membranes in the absence of amyloid peptides. He explained that a solvent called Hexafluoroisopropanol, or HFIP, used to prepare amyloid peptides for research experiments, caused the membrane thinning seen in past studies designed to show how Alzheimer’s disease cause brain cell death.

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"HFIP is a good solvent used to break up clumps of the peptide to prepare for experiments, but it's toxic and membrane-active. What we found was that the reported preparation procedure did not remove the solvent effectively. Our findings are watertight since we could reproduce the thinning effect in the absence of amyloid-beta peptides by this solvent alone."

The scientists believe their findings will make Alzheimer’s disease more treatable, perhaps with drugs that block calcium ions from entering the cell membrane and killing brain cells.

"When you understand these mechanisms better, you have a better chance of being able to pharmaceutically counteract them as a possible treatment. For instance, if amyloid-beta thins membranes, this general effect might be difficult to treat. On the other hand, if it forms pores, this effect might be treatable with pore blockers. Ion channel blockers are medications sold today to treat a variety of diseases,” Mayer said.

The discovery of how amyloid peptides kill brain cells by poking holes in the cell membranes, should lead to tremendous progress in the treatment of Alzheimer’s disease.