New focus for Seattle philanthropist, whose mother suffered from the mind-robbing disorder that afflicts 5.3 million Americans.

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For Microsoft co-founder Paul Allen, the quest to understand the human brain is more than an academic pursuit. For nearly a decade before her death, Allen saw his mother — a librarian with a keen intellect and a passion for learning — struggle with Alzheimer’s disease.

Now, the Seattle billionaire is making his first foray into the field of Alzheimer’s research, announcing several grants for projects with the potential to yield new approaches to a disease that remains tough to diagnose and impossible to treat.

Totaling $7 million, the new grants are small compared to the nearly half a billion dollars Allen has plowed into the Seattle-based Allen Institute for Brain Science, which focuses on basic brain biology. But the goal with the Allen Distinguished Investigator grants is to catalyze breakthroughs by funding ideas considered too edgy for traditional funders.

“They put a call out for people willing to take some chances and try something crazy,” said Jeff Iliff, of Oregon Health & Science University, in Portland. He and his colleague William Rooney got $1.4 million to determine whether aging makes people more vulnerable by disrupting a natural housecleaning system in the brain.

Another project will use stem cells to generate neurons that can be grown in a test tube, then analyzed to see which genes are switched off or on in normal versus diseased cells.

A group at the University of Cambridge in the U.K. plans to probe the brain’s mysterious white matter, which may play a key role in the spread of the protein tangles and plaques common in the brains of Alzheimer’s patients. One of the wildest ideas comes from Dr. Aimee Kao, of the University of California, San Francisco. She suspects that tiny changes in pH — the degree of acidity or alkalinity — inside cells might be what allows the formation of plaques and tangles.

“It’s a very young idea,” said Judy Lytle, medical research program officer for the Paul G. Allen Family Foundation. “But it’s something that could have a very broad impact in terms of pH being important in every cell of the body.”

In the past, Allen, who owns the Seattle Seahawks football team, has also backed research on concussions, in addition to his support for the brain institute. But it took a while to figure out how to approach Alzheimer’s, a field that already attracts a lot of attention from scientists around the world, Lytle said.

“He likes to fund things that other people won’t, that might be a little riskier,” she said. But if they succeed, the payoff can be greater than from the kinds of incremental studies favored by the National Institutes of Health and other federal agencies.

Iliff’s work falls squarely in the “risky” category.

He and his colleagues recently discovered a system in the brains of mice that flushes out toxic proteins and other waste materials while the animals sleep. They also found that in older mice and in mice with brain injuries, that housekeeping system didn’t function as well, which might be a factor in allowing protein tangles and plaques to build up.

But they don’t know yet if a similar system exists in humans — and that’s what they will use the Allen funding to try to find out.

“The first step is to see if we can image this cleaning system in the brains of sleeping humans,” Iliff said. If so, the next steps will focus on the way aging affects the system.

“This is the sort of project that more conservative funding, through the federal government, would never touch,” he said.

Alzheimer’s is the sixth leading cause of death in the United States, and the number of cases is projected to skyrocket as the population ages. Yet the federal government invests only about $600 million a year in Alzheimer’s studies, compared with more than $2 billion for AIDS and $6 billion for cancer, said Dean Hartley, director of science initiatives at the Alzheimer’s Association.

That disparity is one reason there are no drugs on the market that significantly slow the disease’s progression or prevent its onset, Hartley said. So his group welcomes Allen’s interest in the field, and helped review the research proposals.

“Alzheimer’s is underfunded, so anytime you bring additional dollars into the field it’s wonderful.”

The slow pace of progress, and funding, is frustrating to scientists who are trying to make a difference now, Iliff said. “I think all of us want to affect Alzheimer’s disease as quickly as possible,” he said. “The Allen folks were interested in funding people willing to try to take one big step, all at once.”

Two conditions of the grants are that each research team must include people from outside the Alzheimer’s field — from computational science, for example — who can contribute new ways of thinking, Lytle said. And the researchers are all required to meet jointly several times during the three-year course of the grants, to share ideas and insights.

That’s something Iliff is looking forward to.

“When you take a couple of these outlandish hypotheses and put them together, it’s very possible some interesting new things will come out of that,” he said.