ANN ARBOR, Mich.---For a decade, Alzheimer's disease researchers have been entrenched in debate about one of the mechanisms believed to be responsible for brain cell death and memory loss in the illness.
Now researchers at the University of Michigan and the University of California, San Diego have settled the dispute. Resolving this controversy improves understanding of the disease and could one day lead to better treatments.
Michael Mayer, an assistant professor in the U-M departments of Biomedical Engineering and Chemical Engineering, and Jerry Yang, an assistant professor in the Department of Chemistry and Biochemistry at UCSD, and their colleagues found a flaw in earlier studies supporting one side of the debate. Their findings are published online in the Journal of Neurotoxicity Research. They will appear in the May print edition.
Their results clarify how small proteins called amyloid-beta peptides damage brain cell membranes, allowing extra calcium ions to enter the neurons. An ion is an electrically-charged particle. An ion imbalance in a cell can trigger its suicide.
Amyloid-beta peptides are the prime suspects for causing cell death in Alzheimer's, although other mechanisms could also be to blame. The disease is not well understood.
The researchers confirmed evidence found by others that amyloid-beta peptides prick pores into brain cell membranes, opening channels where calcium ions can rush in. This was one mechanism the field had contemplated, but other evidence suggested a different scenario. Some researchers believed that the peptide caused a general thinning of the cell membranes and these thinned membranes lost their ability to keep calcium ions out of brain cells. Mayer and Yang disproved this latter theory.
"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. He cautions that much research is needed before it is known whether such medications are effective and safe to treat Alzheimer's.
Mayer and Yang were able to explain the other experimental results that blamed cell membrane thinning for uncontrolled calcium ion fluctuations. It turns out that in these studies, trace amounts of residual solvent used to prepare the peptide had a dramatic effect. The Michigan- and UCSD-led team reproduced these experimental results using only the solvent, without the peptide. The solvent is called Hexafluoroisopropanol, or HFIP.
"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," Mayer said. "Our findings are watertight since we could reproduce the thinning effect in the absence of amyloid-beta peptides by this solvent alone."
Yang and Mayer carried out these experiments by examining how the electric current fluctuates across artificial membranes and live human cancer cell membranes in the presence of the amyloid-beta peptide. (Cancer cells are often used in biological experiments because they reproduce rapidly.) 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 measuring across the cell membrane 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.
"This ongoing controversy has slowed our own progress in Alzheimer's research as well as progress in other labs," Mayer said. "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."
The paper is called "Amyloid-beta-induced ion flux in artificial lipid bilayers and neuronal cells: Resolving a controversy." Members of Mayer's and Yang's research groups contributed to this study, as did the research group of R. Scott Turner, an associate professor of neurology at the U-M Medical School. The research is funded by the Wallace H. Coulter Foundation, the National Science Foundation, the Alzheimer's Disease Research Center and the Alzheimer's Association. U-M has filed for patent protection on this research, and it is seeking licensing partners to help bring the technology to market.
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The University of Michigan College of Engineering is ranked among the top engineering schools in the country. At more than $130 million annually, its engineering research budget is one of largest of any public university. Michigan Engineering is home to 11 academic departments and a National Science Foundation Engineering Research Center. The college plays a leading role in the Michigan Memorial Phoenix Energy Institute and hosts the world class Lurie Nanofabrication Facility. For more information: http://www.engin.umich.edu/.
Wind turbines causing health problems, some Ontario residents say
Noise and vibrations caused by wind turbines are causing sleep disruptions and other health problems among people who live nearby, some Ontario residents say.
"I'm very concerned about the victims that we've got in Ontario because they're really suffering some pretty significant, adverse health effects," said Carmen Krogh, a retired Alberta pharmacist who is conducting a survey of people living near wind turbines.
Krogh, who now lives in Cormac, Ont., about 130 kilometres west of Ottawa, said she once fell ill while vacationing near a wind turbine complex in 2005. Initially, the turbines weren't moving, but once the wind picked up the blades started turning. Within 10 minutes she began to experience vibrations through her body, an intense headache, queasiness, dizziness and heart rhythm irregularities, she told CBC's The Current on Tuesday.
"It was like my heart was trying to beat to the time of the blades."
'These three behind us here sound literally like this house is in a washing machine.'— Barbara Ashbee, who lives near a wind farm
The symptoms subsided after she left the area.
Since then, Krogh said, she has heard many stories from other people who say they have fallen ill as a result of wind turbines. She is currently distributing questionnaires in areas with wind turbines, asking residents to describe whether they have experienced any effects from the turbines, and if so, what those might be. "We need some kind of vigilance program so people can report their adverse effects," she said.
Krogh is not the only person to document illness caused by wind turbine noise. Last year, Dr. Nina Pierpoint, a researcher at the Johns Hopkins University School of Medicine, published a book called Wind Turbine Syndrome describing symptoms reported by people who live near wind turbines in the United States.
In March, Dr. Michael A. Nissenbaum, a radiologist at the Northern Maine Medical Center, presented to the Maine Medical Association the results of 15 interviews of people who lived near a wind farm in Mars Hill, Maine, which found that many began experiencing sleep disturbances, headaches, dizziness, weight changes, possible increases in blood pressure, and increased prescription medication use after the turbines were turned on.
No peer-reviewed evidence: wind industry
Whittaker acknowledged that wind turbines are a fairly new energy technology that barely existed in Canada 10 years ago.
"So it's natural that people are going to have questions, that they're going to have concerns." Barbara Ashbee and Denis Lormand, a retired couple who live near a wind farm outside Shelburne, Ont., about 75 kilometres northwest of Toronto, initially didn't have concerns when wind turbines were erected near their home. The nearest is 450 metres away.
"I thought they were going to be good for the environment, for the province and Canada and the whole world, really," said Ashbee. "But I also thought they were quiet and passive."
In fact, the turbines often cause a loud whooshing noise that can be heard throughout their house, they said. "It's disturbing, it's distressing, it's totally consumed us for four months," said Ashbee.
"You can't sleep properly, you can't do your work properly … you even lose desire to do the normal, everyday things."
Constant, cyclical noise
Lormand said the noise also keeps him awake at night and causes a ringing in his ears. At other times, a low vibration comes through the walls and through Ashbee's pillow when she's trying to sleep, forcing her to get up and turn the television on in an effort to drown it out.
Geoff Leventhall, an Ontario consultant who provides analysis and advice concerning noise, vibrations and acoustics, said low-frequency wind turbine noise is below the limit of human hearing.
"We are not hearing them and I don't believe they are having any effect on us," he said, adding that wind turbine noise in general is no different from any other kind of noise.
Whether the noise is different from other noises or not, it has disturbed Ashbee and Lormand to the point that the couple plan to move.
"We've really tried hard to fix things," Ashbee said. "I don't think it's fixable."
Krogh said she thinks there need to be more evidence-based studies on the health effects of wind turbine noise and in the meantime the Ministry of the Environment should impose stricter guidelines for how far the turbines must be from homes. She added that she has raised her concerns with the wind energy industry but they deny there is a problem.
"And I would expect that," she said. "It's pretty hard to tell people that their product might make people sick."