Chicago :
Alzheimer's researchers at Harvard for the first time are scanning the brains of healthy patients for the presence of a hallmark protein called tau, which forms toxic tangles of nerve fibers associated with the fatal disease.
The new scans are part of a large clinical trial called Anti-Amyloid Treatment in Asymptomatic Alzheimer's or A4, the first designed to identify and treat patients in the earliest stages of Alzheimer's, before memory loss begins.
Patients accepted into the A4 trial already have deposits of beta amyloid, the other protein associated with Alzheimer's. The addition of the tau scan will allow scientists to get a much clearer picture of the events that lead to Alzheimer's. Thedisease affects 5 million Americans, and 16 million are projected to be afflicted by 2050.
Dr. Reisa Sperling of Massachusetts General Hospital in Boston, who is leading the 1,000-patient trial, said tau is commonly found in small amounts in healthy people over age 70, but it is generally confined to an area of the brain called the medial temporal lobe.
When amyloid is present, it somehow opens the door for tau to spread to other parts of the brain, causing widespread cell death and cognitive decline.
"Tau is the actual bad actor on the front line that tears up the brain. Being able to see it in living humans is a breakthrough," said Dr. Keith Johnson, director of molecular neuroimaging at Massachusetts General, who is leading the imaging portion of the A4 trial.
In the study, patients will be offered treatments to remove amyloid from the brain in the hopes of keeping tau in check.
Several companies have developed drugs aiming to remove amyloid and alter the course of Alzheimer's, but all failed to show a significant benefit. Sperling and other researchers believe that's because the drugs were introduced too late after the onset of disease.
In 2012, Eli Lilly's solanezumab failed to slow the disease in patients with two trials of patients with mild to moderate symptoms. But combined results showed the drug appeared to slow cognitive decline by 34 percent among patients who started with only mild symptoms.
Patients in the A4 trial will be randomized to receive Lilly's anti-amyloid drug or a placebo for about three years. Lilly is funding the trial, along with the National Institutes of Health and several philanthropic organizations.
Researchers plan to do tau imaging on up to 500 patients in the A4 trial. The tau imaging will be paid for by the Accelerating Medicines Partnership, which is sponsored by the National Institutes of Health and the Alzheimer's Association.
Arthur Canter, 67, a retired executive from Boston, will be the first A4 patient to be scanned for tau. Canter, who has a sharp memory and quick wit, already has amyloid building up in his brain.
Canter will get his scan today and fully expects it will show deposits of tau forming as well. His mother, 91, has Alzheimer's, and his father showed signs of dementia when he died in his 70s from an unrelated condition.
"My assumption, predicated on my own genetics, is that I am likely to be get Alzheimer's. In this regard, I'd rather hit it head on," he said.
© Thomson Reuters 2015
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