Protein is found to be key in slowing the progression of Alzheimer’s disease.
Published in Brain and led by University of Cincinnati researcher Dr. Alberto Espay, a new research study challenges long-held assumptions about Alzheimer’s treatment, particularly the role of amyloid plaques in the disease’s progression. For years, the dominant theory in Alzheimer’s research has focused on amyloid-beta 42 (Aβ42), a protein that forms clumps, or amyloid plaques, in the brain. These plaques were believed to damage neurons and lead to the cognitive decline characteristic of Alzheimer’s disease. However, Dr. Espay’s team has introduced a new perspective. Instead of focusing solely on the plaques, they proposed that soluble Aβ42 plays an essential role in maintaining neuron health, and it is the loss of this soluble protein that leads to dementia, not necessarily the buildup of plaques.
The research suggests that amyloid plaques may be a normal response to stressors in the brain, such as biological, metabolic, or infectious changes.
“Most of us will accumulate amyloid plaques as we age,” explained Espay. “Yet, many people with these plaques do not develop dementia.” This observation raises questions about whether targeting amyloid plaques is the right approach for slowing Alzheimer’s progression.
The study sheds light on monoclonal antibody treatments, which are designed to remove amyloid plaques from the brain. These treatments have recently gained approval after demonstrating some effectiveness in maintaining cognitive health, slowing decline. However, the team noticed something not initially expected: While these treatments removed amyloid plaques, they also inadvertently increased levels of soluble Aβ42. This increase in Aβ42, rather than the removal of plaques, seemed to correlate with cognitive improvements in patients.
Data from nearly 26,000 patients was examined. These patients participated in 24 different clinical trials involving the antibody treatments. They compared cognitive outcomes with changes in Aβ42 levels before and after treatment. Their findings revealed a strong link between higher post-treatment Aβ42 levels and a slower progression of cognitive decline. In other words, cognitive improvements could be predicted just as well by increases in Aβ42 as by reductions in amyloid plaques.
Espay acknowledged that the dual effects of these treatments – reducing amyloid plaques while boosting Aβ42 – create a dilemma.
“Our study shows that cognitive benefits might stem from increasing Aβ42 rather than just decreasing amyloid,” he noted.
This presents a challenge for clinicians, as removing amyloid from the brain might accelerate brain shrinkage, potentially worsening other aspects of Alzheimer’s.
Espay posed the question, “Do we continue giving patients treatments that reduce amyloid, knowing they increase Aβ42? Or should we focus on therapies that directly raise Aβ42 without targeting amyloid?”.
As research continues, Espay remains hopeful that the findings will guide the development of new therapies that better address the underlying causes of Alzheimer’s, maintaining cognitive health for a longer period of time. His team is already exploring options for increasing Aβ42 levels in patients without relying on amyloid-targeting drugs. The potential to slow or even halt cognitive decline altogether by restoring this protein could mark a turning point in the battle against this disease.
Sources:
Alzheimer’s disease could be slowed by boosting a certain protein in the brain, researchers say
Boosting brain protein levels may slow decline from Alzheimer’s
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