Alzheimer's decline may be slowed by protein boost

National media outlets including Newsweek and U.S. News & World Report highlighted UC research led by Alberto Espay that found new monoclonal antibody drugs for Alzheimer’s may slow cognitive impairment through boosting levels of the protein Aβ42 in the brain. 

The research was published in the journal Brain Sept. 11.

For decades, the prevailing theory in the field has stated that a protein made up of 42 amino acids called amyloid-beta 42 (Aβ42) hardens into clumps called amyloid plaques, and those plaques in the brain cause the damage and/or dysfunction that causes Alzheimer’s disease.

Espay and team have hypothesized that normal, soluble Aβ42 in the brain is crucial for neuron health and that the loss of Aβ42, rather than the buildup of plaques, drives Alzheimer’s. This includes published research that suggests dementia occurs not when plaque levels are high but when Aβ42 levels drop very low. 

"We noticed that most of the population with amyloid plaques does not develop Alzheimer's," Alberto Espay, professor of neurology at the University of Cincinnati Academic Health Center, told Newsweek. "By the age of 85 years, only one fifth of those with amyloid plaques develop Alzheimer's disease."

The team analyzed data from nearly 26,000 patients enrolled in 24 randomized clinical trials of new antibody treatments, assessing cognitive impairment and differences in levels of Aβ42 before and after treatment. They found that higher levels of Aβ42 after treatment were independently associated with slower cognitive impairment and clinical decline.  

Espay said these findings fit well into his larger hypothesis about the root cause of Alzheimer’s, as increasing levels of Aβ42 appear to improve cognition.  

"All stories have two sides—even the one we have told ourselves about how anti-amyloid treatments work: by lowering amyloid," Espay said. "In fact, they also raise the levels of Aβ42. Even if this is unintended, it is why there may be a benefit. Our study shows that we can predict changes in cognitive outcomes in anti-amyloid trials at least as well by the increases in Aβ42 as by the decreases in amyloid."

Read the Newsweek article.

Read the U.S. News & World Report article, originally published on HealthDay.

Read more about the research.

Featured photo at top of Alberto Espay. Photo/University of Cincinnati.