After looking at a thousand human brains over nearly a decade, Montreal researchers have found a genetic variation that delays the onset of Alzheimer’s disease by as many as five years.
Researchers are particularly excited because the gene in question regulates cholesterol, already the focus of heavy research and a target for drug development. This latest finding provides genetic support for the idea that Alzheimer’s can be prevented by inhibiting the cholesterol-regulating gene.
“It’s a very good study,” said Weihong Song, Canada Research Chair in Alzheimer’s disease. The research provides “new insight into the molecular mechanism leading to Alzheimer’s disease.”
The research was performed by Judes Poirier and his team at the Douglas Mental Health University Institute. They found that a variant of a cholesterol-regulating gene, which makes the enzyme HMG CoA reductase, delays the onset of Alzheimer’s.
“If you have [the variant], the disease will start roughly four to five years later,” said Dr. Poirier, lead author of the study published Tuesday in Molecular Psychiatry. About a quarter of the population carries the variation, but a drug could potentially be developed to mimic the effect of the variation in non-carriers.
Scientists already know a lot about HMG CoA reductase – this enzyme, responsible for deciding whether or not the body makes cholesterol, is inhibited by a group of drugs called statins, better known for their role in fighting heart disease. Most people think of heart disease when they hear the word cholesterol, but it plays a huge role in the brain as well.
“The brain is the organ with the highest concentration of cholesterol in the entire body,” Dr. Poirier said.
Even though the brain is only 2 per cent of our total body mass, it contains 25 per cent of all our cholesterol. That’s because the brain is full of neurons that send information to each other and all these connections are insulated by cholesterol.
The Alzheimer’s community has long known about a link between cholesterol and the disease. Some research has found that high cholesterol levels may raise the risk of Alzheimer’s. Previous correlational studies have found that users of old varieties of statins had less Alzheimer’s disease than non-users.
The next step is to develop a brain-specific statin and run a trial to confirm whether or not it consistently delays the onset of Alzheimer’s. But it may be difficult to find funding for a multimillion-dollar drug trial.
“These [old statin] patents are no longer alive. These drugs are sold by generic companies,” Dr. Poirier said. “No patent, no profit. I’ll be pushing very hard for a preventative small-scale trial that will examine a cholesterol drug that can enter the brain.”
At least one funding organization is interested in the research. The discovery “could draw us closer to disabling this devastating disease,” said Mimi Lowi-Young, CEO of Alzheimer Society of Canada, in an e-mail. “The Alzheimer Society looks forward to working with Judes [Poirier] on this latest development so we can get to more effective treatments faster.”
There is no current prophylactic treatment for the neurological disease that affects 747,000 Canadians. Dr. Poirier estimates that more than 100 potential Alzheimer’s drugs have been tested and failed in the past 15 years.
The number of Canadians with the disease is expected to double by 2031. Annual spending on dementia, including Alzheimer’s, is estimated to reach nearly $300-billion by 2040.
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