New findings about differences between teen and elderly brains have opened new paths to treating Alzheimer's

Forgetting things is a natural, lifelong process that slows down rather than advances with age, a recent finding that stunned Marin County researchers and opened a new approach to treating Alzheimer's disease.

Young people are actually more forgetful than their elders, even those afflicted with Alzheimer's, a degenerative brain disorder that leads to dementia and death.

What sets younger people apart is the "plasticity" of their gray matter, enabling them to create new memories as fast as they break old ones, maintaining a mental balance, said Dr. Dale Bredesen, leader of an Alzheimer's research group at the Buck Institute in Novato.

"Young people are unlearning things more quickly than older adults," said Bredesen, a physician who is also Buck's chief executive officer. "The key here is the balance."

"I would agree with that," said Tiffany Fisher, 21, a Santa Rosa Junior College sophomore. "I have a terrible memory."

Fisher said she's great at recalling things she's currently involved in, such as her studies and student government issues, but finds memories from high school and childhood slipping away.

Comparing the brain to an automobile, Bredesen said that young minds like Fisher's run like a Ferrari, effortlessly shifting between making and breaking memories.

In older people, the brain slows in both directions, he said, and in those with Alzheimer's it gets "stuck in reverse," obliterating the balance between forgetting and remembering.

Alzheimer's afflicts more than 5 million Americans, a number that is expected to double or triple by the year 2050 unless a cure or treatment is discovered. The disease kills 66,000 people a year, and the cost of treating and caring for patients with Alzheimer's and other dementias is more than $148 billion a year.

Scientists cannot yet measure precisely the memories in the brain after life has ended, but they now believe they can quantify its losses. Peeling open and staining the brains of deceased people, Bredesen and his colleagues counted the number of places where a particular kind of disruption had occurred in a protein found in long, stringy brain cells called neurons.

Those disruptions, called cleavage of the amyloid precursor protein, underlie the "molecular mechanism" of memory loss, he said.

Elderly people -- in their 60s, 70s and 80s -- with Alzheimer's had four times as much protein cleavage as seniors with no disease. But the startling find, Bredesen said, was that normal young people -- in their 20s, 30s and 40s -- had 40 times as much protein cleavage as normal seniors (60s to 80s) and 10 times as much as the elderly Alzheimer's victims.

"At first I had thought the young (brain) would never be doing this," he said.

The Buck study, published earlier this month in the Journal of Alzheimer's Disease, revolutionizes thinking about the disease, Bredesen said.

"Scientists consider Alzheimer's to be an alien process, but we now believe that it is the result of an imbalance in two totally normal processes -- memory making and memory reorganization, which together constitute plasticity" in a healthy brain, young or old.

In Alzheimer's, a "molecular shifting switch" cuts off the memory-making process, Bredesen explained, "throwing the balance of making and breaking memories seriously off kilter."

"Now we see this disease in a very different light," he said.

The finding is therapeutically important because it suggests a new route to preventing Alzheimer's by disconnecting the switch, he said.

Through genetic engineering, Buck researchers have been able to turn that switch off in mice that were bred to develop Alzheimer's. For humans, they are now trying to find a medicine that will do the same.

It would take three to five years for any formulation to be adopted as an Alzheimer's therapy or cure, Bredesen said.

The Buck research center, opened in 1999 in the hills above Novato, was the first independent facility in the U.S. to focus solely on aging and age-related conditions including Alzheimer's and Parkinson's disease, cancer, stroke and arthritis.

In 2005, it was designated by the National Institutes of Health as one of five national centers of excellence in research on aging.

For Fisher, the junior college student, word that forgetfulness is normal at her age comes as a big relief.

"I don't feel so much like an idiot anymore," she said.

You can reach Staff Writer Guy Kovner at 521-5457 or guy.kovner@pressdemocrat.com.