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Unraveling Alzheimer's mysteries in search of new treatment

Over the past several decades scientists have begun to unravel the complicated process that leads to the death of brain cells and, ultimately, the disease we call Alzheimer’s. That new understanding may lead to therapies that can halt the disease before symptoms appear and brains are irreparably damaged. Washington University researchers have tracked the course of Alzheimer’s by studying a gro
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Over the past several decades scientists have begun to unravel the complicated process that leads to the death of brain cells and, ultimately, the disease we call Alzheimer’s. That new understanding may lead to therapies that can halt the disease before symptoms appear and brains are irreparably damaged.

Washington University researchers have tracked the course of Alzheimer’s by studying a group of 128 people at risk for carrying the genes for a rare inherited form of the disease for the past four years. The research has shown that Alzheimer’s is already taking a toll on the brain decades before people start to experience symptoms. Meanwhile, Mayo Clinic researchers are tracking thousands of people with no genetic predisposition and no signs of disease to see if and when the disease appears what early signs might have predicted it. Some of the Mayo Clinic’s findings mirror those from the genetic Alzheimer’s research.

Scientists have long known that the main culprits in Alzheimer’s are two proteins that gunk up the brain: autopsy studies performed over a century ago showed plaques of sticky amyloid protein clogging the spaces between nerve cells, while tangles of twisted tau protein threads were destroying cells from within.

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What no one knew was how and when the process began. That’s why an international team of scientists opted to study people with an inherited form of Alzheimer’s.

Dr. John Morris, Friedman Distinguished Professor of Neurology and director of the Knight Alzheimer’s Disease Research Center at Washington University, said the international study, called the “Dominantly Inherited Alzheimer Network,” or DIAN, looks at people who are destined to develop symptoms of Alzheimer’s disease because they inherited a gene mutation that causes the illness.

Because DIAN volunteers who have the gene mutation will eventually develop Alzheimer’s disease by a certain age, researchers were able to start observing them well before symptoms would have developed.

As it turned out, 88 of the 128 volunteers were carriers of the genetic mutations, while the other 40 were not.

To document changes that might presage the disease, Morris and his colleagues used PET scanners to look for amyloid deposits and to evaluate glucose use, which tends to go down as the brain is attacked by the disease.

MRI scans were used to determine whether there was any brain atrophy, while cerebrospinal fluid was tested for tau levels. 

The volunteers were also given a battery of neuropsychological tests to determine whether they were showing any signs of mental deterioration. 

“We have found that the brain changes of Alzheimer’s disease begin maybe 20, possibly 25 years before we expect individuals to develop symptoms of dementia,” Morris told TODAY. “We have learned which of the brain changes start first so we get a clue as to what starts the illness and then we can follow along to see what other abnormalities occur before the onset of symptoms.”

Morris can’t say for sure, but hopes that those without the inherited mutations may benefit from the study’s findings: What remains to be determined is how closely inherited Alzheimer’s resembles the more common form.

The hope is that the biomarkers identified by Morris and his colleagues will also help predict cases of the sporadic disease. Morris said it also showed “there is a window of perhaps two decades where we might intervene with therapeutic strategies to try to delay or even prevent the onset of Alzheimer’s disease dementia.”

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If the biomarkers found by the researchers also apply to the more common forms of Alzheimer’s then it may be possible to determine who is likely to develop the disease years before it wreaks havoc on the brain.

That’s very good news given the discouraging results of trials that looked at therapies to treat individuals who already had developed symptoms of dementia.

Morris and colleague Dr. Randall Bateman, Joanne Knight Distinguished Professor of Neurology at Washington University, have designed an ongoing clinical trial to test drugs that block amyloid in some of the DIAN volunteers who have yet to develop symptoms.

“This is a true advance in the field,” Morris told TODAY. “Never before have people who don’t have the symptoms of Alzheimer’s disease been given medications.”

The only caveat to the DIAN research is that no one knows yet whether the findings can be applied to people who develop the disease sporadically.

The answer to that question may come from the Mayo Clinic where Dr. Ronald Petersen is studying individuals with memory and cognitive problems due to mild cognitive impairment (MCI), a condition that often leads to the development of Alzheimer’s.

Petersen and his colleagues are following 4,000 healthy people aged 50 to 90 drawn from small towns, urban and rural environments.

They are beginning to isolate biomarkers that predict who is at a greater risk of developing MCI and Alzheimer’s disease.

Petersen, director of the Mayo Alzheimer Research Center, believes that sporadic Alzheimer’s – which is far more common than the inherited version of the disease – is the more complicated form.

While a therapy that targets amyloid may help those with the familial form of the disease, Petersen believes that therapies for sporadic Alzheimer’s may need to be more complicated because more aberrant proteins are involved, as well as vascular disease in some cases.

“Ultimately we may have specific biomarkers for each of the components,” he told NBCNews.com. “And it may take a cocktail of medications to treat someone with typical Alzheimer’s, just like you need a cocktail to treat diseases like hypertension and HIV. I don’t think there is going to be a single silver bullet that treats Alzheimer’s.”

For more information, visit the Alzheimer's Association or call their toll-free hotline at 1-800-272-3900.