Boosting a specific brain protein could potentially slow down the progression of Alzheimer’s disease, according to a recent study conducted by researchers at the University of Cincinnati. The traditional belief has been that Alzheimer’s is triggered when a protein known as amyloid-beta 42 (Aβ42) forms into plaques that accumulate in the brain, causing harm to neural cells and resulting in cognitive decline. However, the researchers at the University of Cincinnati have proposed a different theory, suggesting that the disease may actually be caused by low levels of healthy, functioning Aβ42.
This new hypothesis is based on the unexpected outcomes observed in recent clinical trials of monoclonal antibody medications such as lecanemab (Leqembi) and donanemab (Kisunla), which have inadvertently led to an increase in levels of the protein in the brain. Lead study author Alberto J. Espay, MD, explained that the higher levels of Aβ42 following treatment were associated with a slower rate of cognitive decline, indicating that restoring this protein to normal levels could be more beneficial for Alzheimer’s patients than simply removing amyloid plaques.
The researchers analyzed data from nearly 26,000 Alzheimer’s patients who participated in 24 randomized clinical trials for the newly approved antibody treatments. By comparing the cognitive abilities of patients before and after taking the medications, they found a correlation between increased Aβ42 levels and a deceleration in cognitive impairment and clinical decline. These findings were published in the medical journal Brain on September 11.
Understanding Amyloid
Contrary to popular belief, amyloid plaques are not necessarily harmful. According to the researchers, these plaques are actually a response of a normally reactive brain to various stressors, including infections, toxins, and biological changes. Amyloid plaques are described as “the tombstones of Aβ42” by Espay, who emphasized that they do not pose a direct threat to the brain.
The study challenges the conventional notion that amyloid plaques are the primary cause of Alzheimer’s disease and that removing them is the key to treatment. Espay noted that while beta amyloid does play a significant role, other factors such as the tau protein, immune system, vascular system, metabolic health, and environmental influences also contribute to the disease process.
Looking Ahead
Moving forward, the University of Cincinnati research team intends to explore therapies that directly increase Aβ42 levels without targeting amyloid. This approach could potentially pave the way for novel treatment strategies for Alzheimer’s disease.
A Complex Disease
Ozama Ismail, PhD, the director of scientific programs at the Alzheimer’s Association in Washington, D.C., commented on the study’s findings, highlighting the complexity of Alzheimer’s disease. While the Aβ42-related hypothesis may offer insights into the progression of the disease, Ismail pointed out that Alzheimer’s is multifaceted and likely involves multiple biological mechanisms.
In addition to beta amyloid, Ismail emphasized the importance of considering other factors such as the tau protein, immune system, vascular system, and metabolic health in understanding Alzheimer’s disease. He advocated for a comprehensive approach to treatment that incorporates various therapies targeting different mechanisms, similar to the management of other complex diseases like diabetes and heart disease.
Limitations and Future Research
Despite the promising results of the study, Espay acknowledged the limitation that individual-level data was not accessible for analysis. However, he assured that the findings were well-supported by the group-level data available.
In conclusion, the study sheds light on the potential role of boosting Aβ42 levels in slowing down Alzheimer’s disease progression, challenging the conventional wisdom surrounding amyloid plaques. As researchers continue to unravel the complexities of the disease, a multifaceted approach to treatment that considers various biological mechanisms may hold the key to developing effective therapies for Alzheimer’s patients.
