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Published on: July 2, 2012
by Michelle Fay Cortez for Businessweek:
Over the past 18 months, 81-year-old Bill Bunnell has visited the doctor a half-dozen times to take memory tests, provide blood samples, and undergo a spinal tap and imaging scans. It’s all part of the most extensive study ever conducted on Alzheimer’s.
Now researchers are about to take an even closer look at Bunnell, a retired engineer from Madison, Connecticut.
Working with $2 million in new grants to be announced this week, the researchers for the Alzheimer’s Disease Neuroimaging Initiative will, for the first time, start mapping the DNA of 800 participants in a study attempting to find the root causes of memory loss. The goal is to see if physical changes from Alzheimer’s can be matched to genetic disparities, which can then be compared with findings from healthy people like Bunnell.
“If there’s ever to be progress in the discovery of the fundamentals that lead to Alzheimer’s, this is the way to do it,” said Aubrey Milunsky, director of the Boston University Center for Human Genetics, which isn’t involved in the research.
The grants are split evenly from the Alzheimer’s Association, a nonprofit health group focused on the care and treatment of people with the disease, and the nonprofit Brin Wojcicki Foundation, a charitable organization created by 23andMe Inc. co-founder Anne Wojcicki and her husband Sergey Brin, co-founder of Mountain View, California-based Google Inc.
The research initiative, funded by the U.S. government, nonprofit groups and private industry, began tracking physical and mental changes in people ages 60 and older in 2004. Alzheimer’s is an irreversible disease that destroys brain cells and makes it difficult for patients to think, remember and function. It afflicts 5.1 million Americans, a number that may grow to 16 million by 2050, according to the U.S. National Institutes of Health.
The ADNI study has sought to tie the development of symptoms to physical changes in people with Alzheimer’s, including deposits of protein tangles and plaque in the brain over time.
By diving deeply into the genetics of healthy people and those with the disease, scientists may find differences that either spur the buildup of the amyloid plaque that’s a hallmark of the disease, or protect people from it.
The genetic samples have already been gathered, the researchers said. They’ll be sequenced at Illumina Inc. (ILMN) (ILMN), the gene-mapping company based in San Diego that fought off a $6.7 billion takeover bid from Roche Holding AG (ROG) earlier this year.
It will take 16 weeks to get the results, which will generate so much information that the data on each participant will be sent to the researchers on separate hard drives. The team is working on ways to share the raw data when it emerges, and is considering alternatives like lending them to investigators the way libraries lend books.
Researchers plan to study the genetic makeup of the participants. While roughly 10 genes are already linked to the condition, crucial details about genetic variations and how they interact remain unknown, said Robert Green, associate director of medicine in the Division of Genetics at Brigham and Women’s Hospital and at Harvard Medical School in Boston.
“Alzheimer’s is one of the many diseases that is starting to reach the point where we can benefit from the explosion of genomic information that’s becoming available,” Green said in a telephone interview. “We still don’t know the entire pathway of what causes it. There are mysteries that likely have to be solved before we have truly effective treatments.”
The results of the genetic tests, as with all the other information gathered by the program investigators, will be available to anyone studying Alzheimer’s, said Mike Weiner, the leader of the initiative from the University of California, San Francisco, in a telephone interview. That promises to speed progress, he said.
Open access helped draw funding to expand the program into genetic testing, said Wojcicki, also chief executive officer of Mountain View, California-based gene-testing company 23andMe.
“For something like Alzheimer’s disease, where there is such a critical need, and where it is so urgent and will impact so many of us, we need as many smart minds as we can find working on it,” Wojcicki said. “I’m a big believer that if we have more data, we can solve our health care problems.”
The 8-year-old program is already a watershed in the history of Alzheimer’s, leading to the publication of nearly 500 research reports, said William Thies, chief medical officer of the Alzheimer’s Association, an early contributor to the initiative.
The integration of patients’ medical history with their genetic makeup will provide an unprecedented view of how Alzheimer’s disease emerges and eventually dominates the mind, Thies said by telephone.
“Until you understand the relationship between basic blocks of genetics and the clinical condition of the patient, you’re not going to get very far,” Thies said. “We believe this is the biggest project of whole genome sequencing in a single disease.”
Most people don’t realize Alzheimer’s is strongly inherited, often because their relatives died before developing it, Weiner said. Existing research looks mainly at snippets of the genetic code where variations are thought to exist, an approach that’s been productive but “hasn’t nailed it,” he said. Looking at the whole genome will provide more answers.
“This is a disease that has the potential to wreck our health-care system, our economy and ruin the lives of increasing numbers of people in the next 50 years,” Thies said. “All that can be avoided if we invest appropriately in research and we have the public volunteering for clinical opportunities.”
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