Researchers from the University of Cincinnati have challenged the prevailing theory that Alzheimer’s disease is solely caused by the build-up of amyloid-beta in the brain. They have provided evidence suggesting that it is actually the lessening of amyloid-beta levels in the brain that leads to cognitive decline. The study, published in the journal Brain, analyzed data from 26,000 people enrolled in clinical trials for new monoclonal antibody treatments for Alzheimer’s disease. Researchers found that higher levels of Aβ42, an important protein for brain health, were associated with slower cognitive impairment and clinical decline. This challenges the idea that amyloid plaques are the main culprit in Alzheimer’s disease.
Alberto Espay, MD, lead author of the study, explained that the brain’s ability to produce enough Aβ42 to keep levels within a normal range is what keeps people with amyloid plaques cognitively normal. This suggests that Alzheimer’s is a process of loss of Aβ42 rather than a gain of amyloid plaques. The findings point to the potential benefit of therapies aimed at increasing Aβ42 directly, rather than indirectly through antibody treatments. David Merrill, MD, PhD, commented that addressing modifiable health factors and adopting healthy habits may also contribute to lowering plaque loads in the brain and increasing soluble Aβ42, improving cognitive function over time.
The study challenges the prevailing belief that Alzheimer’s disease is solely caused by the build-up of amyloid-beta plaques in the brain. Instead, the findings suggest that increased levels of amyloid-beta may actually result in less cognitive decline. The researchers analyzed data from clinical trials for new monoclonal antibody treatments for Alzheimer’s disease and found that higher levels of Aβ42, a brain health protein, were associated with slower cognitive impairment and clinical decline. This highlights the importance of maintaining normal levels of Aβ42 in the brain for cognitive health.
The study’s lead author, Alberto Espay, MD, emphasized the importance of brain’s ability to produce enough Aβ42 to keep levels within a normal range in preventing cognitive decline in individuals with amyloid plaques. He suggested that future therapies should focus on directly increasing Aβ42 levels rather than indirectly through antibody treatments. David Merrill, MD, PhD, pointed out the significance of addressing modifiable health factors and adopting healthy habits to lower plaque loads in the brain and increase soluble Aβ42, leading to improved cognitive function over time.
Karen D. Sullivan, PhD, ABPP, expressed that the study’s findings represent a significant shift in the understanding of Alzheimer’s disease. She highlighted the potential controversy and heated discussions that may arise in the neuroscience community as a result of these findings. The study has the potential to spark new research directions and further investigations into the role of amyloid-beta in Alzheimer’s disease. Researchers and experts in the field are advocating for a broader exploration of modifiable risk factors and non-drug approaches to decrease dementia risk and improve cognitive function over time.
