Age-Related Increase in Clearance Time for Amyloid Protein

The amyloid associated with Alzheimer's disease builds up with age, and much more so in people eventually diagnosed with Alzheimer's. Many lines of evidence indicate that the underlying problem is one of slowly failing clearance of amyloid proteins: various systems and mechanisms falter with age due the accumulation of cell and tissue damage. Until amyloid proteins gather in large enough numbers to form lasting clumps, their presence are fairly dynamic, created and cleared on a timescale of hours. Researchers here provide direct evidence of slower clearance rates in older people:

The greatest risk factor for Alzheimer's disease is advancing age. After 65, the risk doubles every five years, and 40 percent or more of people 85 and older are estimated to be living with the devastating condition. Researchers have identified some of the key changes in the aging brain that lead to the increased risk. The changes center on amyloid beta 42, a main ingredient of Alzheimer's brain plaques. The protein, a natural byproduct of brain activity, normally is cleared from the brain before it can clump together into plaques. Scientists long have suspected it is a primary driver of the disease. "We found that people in their 30s typically take about four hours to clear half the amyloid beta 42 from the brain. In this new study, we show that at over 80 years old, it takes more than 10 hours." The slowdown in clearance results in rising levels of amyloid beta 42 in the brain. Higher levels of the protein increase the chances that it will clump together to form Alzheimer's plaques.

For the study, the researchers tested 100 volunteers ages 60 to 87. Half had clinical signs of Alzheimer's disease, such as memory problems. Plaques had begun to form in the brains of 62 participants. The subjects were given detailed mental and physical evaluations, including brain scans to check for the presence of plaques. The researchers also studied participants' cerebrospinal fluids using a technology known as stable isotope-linked kinetics (SILK), which allowed the researchers to monitor the body's production and clearance of amyloid beta 42 and other proteins.

In patients with evidence of plaques, the researchers observed that amyloid beta 42 appears to be more likely to drop out of the fluid that bathes the brain and clump together into plaques. Reduced clearance rates of amyloid beta 42, such as those seen in older participants, were associated with clinical symptoms of Alzheimer's disease, such as memory loss, dementia and personality changes. Scientists believe the brain disposes of amyloid beta in four ways: by moving it into the spine, pushing it across the blood-brain barrier, breaking it down or absorbing it with other proteins, or depositing it into plaques. "Through additional studies like this, we're hoping to identify which of the first three channels for amyloid beta disposal are slowing down as the brain ages. That may help us in our efforts to develop new treatments."



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