Why the Aging Brain Is More Vulnerable to Alzheimer's
by Dennis Thompson for HealthDay:
Age is the greatest risk factor for Alzheimer's disease, and researchers now think they know why that's the case.
New cutting-edge technology reveals that as you age, your brain becomes less and less capable of flushing away a toxic waste product of brain activity called beta-amyloid, the researchers said.
Beta-amyloid proteins can clump together, forming larger amyloid plaques in the spaces between neurons. These amyloid plaques are a hallmark of Alzheimer's disease, the most common form of dementia.
"This is a clue as to why age is the number one, two and three risk factor for Alzheimer's disease," said study senior author Dr. Randall Bateman, director of the Dominantly Inherited Alzheimer Network Trials Unit at the Washington University School of Medicine in St. Louis. "As we slow down our ability to clear away these sticky proteins, the risk of having these sticky proteins build up in the brain goes up and up as we age."
Using this knowledge, future research might come up with a medication or therapy that increases the brain's ability to flush out beta-amyloid, thus reducing or eliminating the risk of Alzheimer's disease, he said.
After age 65, the risk of Alzheimer's disease doubles every five years, the researchers said in background information with the study. At least two out of five people 85 and older are living with the devastating condition.
Keith Fargo, director of scientific programs and outreach for the Alzheimer's Association, said, "We've known for a long time that age is the primary risk factor for Alzheimer's disease. What we haven't known is why."
The body builds all of its proteins -- including beta-amyloid -- by using amino acids as the building blocks.
"We all have amyloid-beta in our brains," Bateman explained. "It's made normally by the thinking cells of our brain, the neurons. They generate amyloid-beta, and the more they fire or communicate with each other -- the more they send little signals to each other -- the more they make."
To explore the effects of age, the researchers used a new technology called stable isotope-linked kinetics (SILK) that allowed them to "tag" amino acids, Bateman said.
The researchers infused the blood of 100 volunteers between ages 60 and 88 with "tagged" amino acids. They then took hourly samples of the patient's cerebrospinal fluid to track the course of beta-amyloid proteins built from those amino acids.
Earlier research had shown that people in their 30s typically take about four hours to clear half the beta-amyloid protein from their brain, Bateman said.
But people 80 or older take about two and a half times longer -- more than 10 hours -- to flush beta-amyloid from their brains, Bateman and his colleagues discovered.
"That's a pure age effect," Bateman said. "It doesn't matter if you have plaques or not. The older you get, the slower it is. And it was highly precisely correlated with age -- we could actually predict what age a person was just based upon how quickly they could clear away amyloid-beta."
In patients who already had evidence of amyloid plaques, the researchers found that their beta-amyloid proteins were more likely to clump together and form those plaques, rather than be flushed out of their brain.
They also learned that reduced flushing of beta-amyloid is associated with clinical symptoms of Alzheimer's disease such as memory loss, dementia and personality changes.
No one is yet sure how the brain disposes of beta-amyloid, Bateman said. It might be flushed out through either blood or spinal fluid, or the brain might have some internal means of breaking down the toxic protein.
But when scientists figure out that mechanism, they might be able to make a drug or a therapy that enhances that process and rids the brain of beta-amyloid faster, Fargo said.
"There's nothing new your doctor is going to have next week based on this, but maybe 10 years from now there will be," he said.
The study was published recently in the journal Annals of Neurology.