A new study published in the journal Brain reveals that increasing levels of a key brain protein might help slow cognitive decline in Alzheimer’s patients.
This finding challenges the long-held belief that reducing amyloid plaques is the best way to treat the disease.
For decades, researchers thought that Alzheimer’s was caused by a protein called amyloid-beta 42 (Aβ42), which clumps together to form plaques in the brain.
These plaques were believed to damage brain cells and lead to memory loss and confusion in people with Alzheimer’s.
However, a team led by Dr. Alberto Espay from the University of Cincinnati has a different theory.
They believe that Aβ42, in its normal, soluble form, is actually important for keeping brain cells healthy.
According to their research, Alzheimer’s doesn’t happen because there are too many plaques, but because the levels of healthy Aβ42 become too low.
Espay’s team found that plaques may actually form as a natural response to stress in the brain, such as infections or toxins.
In fact, most people develop amyloid plaques as they age, but very few go on to develop Alzheimer’s. This suggests that the plaques themselves may not be the main cause of the disease.
Recently, new drugs called monoclonal antibodies have been developed to remove amyloid plaques from the brain. These drugs were approved after clinical trials showed they slowed cognitive decline.
But Espay and his colleagues noticed something interesting in these trials: while the drugs were removing plaques, they were also unintentionally increasing the levels of Aβ42 in the brain.
Espay explained that the brain might produce too much amyloid during times of stress, which lowers the amount of Aβ42. When Aβ42 levels drop below a certain point, dementia symptoms start to appear.
The researchers looked at data from almost 26,000 patients in 24 clinical trials to see if raising Aβ42 levels might improve cognitive function.
Their analysis showed that patients who had higher levels of Aβ42 after treatment experienced slower cognitive decline.
This suggests that the increase in Aβ42, rather than the reduction in plaques, may be responsible for the cognitive benefits of the new drugs.
“If Alzheimer’s is caused by the loss of normal Aβ42, then raising its levels should help, and our study shows that it does,” Espay said. “The key is getting Aβ42 levels back into the normal range.”
However, Espay also pointed out a problem: removing amyloid plaques from the brain can be harmful, potentially causing the brain to shrink faster after treatment. This raises the question of whether reducing amyloid is worth the risk, even if it does increase Aβ42 levels.
Espay and his team are now focusing on developing treatments that can raise Aβ42 levels directly, without targeting amyloid plaques. This new approach may offer a safer and more effective way to slow Alzheimer’s disease.
Source: University of Cincinnati.
