A group of investigators report that they have resolved a controversy regarding how amyloid-beta damages brain cells. Their work clarified that amyloid-beta creates holes in brain cell membranes, which allows calcium ions to enter. The researchers say that the alternative suggestion that amyloid-beta makes the membranes thinner and thus susceptible to calcium ions is untrue.
The study, conducted by scientists from the University of Michigan (UM) and the University of California, San Diego, is published online in the Journal of Neurotoxicity Research. The paper is called “Amyloid-beta-induced ion flux in artificial lipid bilayers and neuronal cells: Resolving a controversy.”
The team explains that previous experimental results that blamed cell membrane thinning for uncontrolled calcium ion fluctuations was because the trace amounts of residual solvent used to prepare the peptide in those studies created the thinning.
In the current investigation, the team used only the solvent called Hexafluoroisopropanol (HFIP) without the peptide. “HFIP is a good solvent used to break up clumps of the peptide to prepare for experiments, but it's toxic and membrane-active,” notes Michael Mayer, an assistant professor in the UM departments of biomedical engineering and chemical engineering.
“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.”
To confirm the other theory that amyloid-beta creates pores in the cell membrane, they studied how the electric current fluctuates across artificial membranes and live human cancer cell membranes in the presence of the amyloid-beta peptide. They also measured the fluctuation of ions in mouse brain cells and in genetically modified mouse brain cells that produce human amyloid-beta peptide.
In all these trials the electrodes registered spikes in electric current consistent with what researchers would expect from the formation of pores in the cell membrane and not from thinning of membranes.
Past Findings in Alzheimer's Research
Researchers Develop Standard of Testing for Alzheimer’s Biomarkers (Mar. 18, 2009)
Two Proteins Working in Tandem Leads to Amyloid Beta Buildup in Alzheimer’s (Dec. 22, 2008)
miRNA Implicated in Inflammation Integral to Alzheimer’s Disease (Nov. 14, 2008)
New Technique Able to Transport Potential Alzheimer’s and Stroke Treatment Past the Blood-Brain Barrier (Nov. 12, 2008)
Fatty-Acid Regulator Associated with Cognitive Function in Alzheimer’s (Oct. 28, 2009)