What will the diagnosis and treatment of Alzheimer’s disease look like 35 years from now?
That was one of the compelling questions tackled during a panel discussion earlier this year at the Partners Innovation World Medical Innovation Forum.
The discussion was inspired by a series of predictions that the noted author Isaac Asimov made in 1984 about what life would be like 35 years later in 2019.
Using Genetics and Family History as a Guide
Rudy Tanzi, PhD, Director of the Genetics and Aging Research Unit at Massachusetts General Hospital, said future success in treating Alzheimer’s disease will come from earlier diagnosis and treatment guided by an individual’s family history and genetic risk factors.
“If you’re in a family with Alzheimer’s disease, look at the earliest age of onset in a first-degree relative. Subtract 20 years and that’s when you want to start looking for problems, because that’s when you want to start treating.”
In contrast to cancer, diabetes and heart disease—where early detection and treatment is key—treatments for Alzheimer’s disease don’t start until patients start showing symptoms of cognitive decline, Tanzi noted. By then, it may be too late to make a difference.
Strategies for Early Intervention
One key to early intervention is to identify imaging or blood tests that can detect the onset of the disease—the formation of amyloid plaques in the brain–10 to 15 years before cognitive symptoms such as confusion and memory loss begin.
Interventions that can slow or halt the formation of these plaques could prevent the chain reaction that leads to more devastating symptoms down the line, Tanzi said. The turning point seems to be when the brain accumulates enough plaques and tangles to prompt the microglia—the brain’s immune cells—to launch an all-out inflammatory attack on both harmful and healthy cells.
“Neuroinflammation at that stage kills at least 10 times more neurons than plaques and tangles, but it’s the plaques and tangles that kill enough neurons early on to trigger the immune system,” Tanzi said.
“I like to say that the plaques are like the match, the tangles are like the brush, but it’s the neuroinflammation that is the forest fire.”
By the time the patient has reached this stage it is likely too late to reverse course. This may be why so many clinical trials for drugs to treat Alzheimer’s patients have failed, Tanzi said.
“We’re taking patients where there is a forest fire blazing and thinking we can just blow out the match, and then we wonder why the trial doesn’t work.”
Tanzi and his colleagues are looking to identify new drugs, repurposed drugs or natural products that might be able to prevent the brain’s microglial cells from reaching that inflammatory tipping point. That point could vary from individual to individual depending on genetics, family history and lifestyle factors.
“We all have our own threshold of when we’re going to trigger neuroinflammation in response to X number of plaques and tangles,” he said.
“In the future we’ll be able to modulate that number through lifestyle modifications and early prevention and not get to that point. Because that is when the brain goes down the slippery slope. “