Increasing levels of a brain protein called Aβ42 may slow the decline of Alzheimer’s disease, a new study suggests.
- Researchers have found that increased levels of the Aβ42 protein in the brain are associated with slower cognitive impairment.
- This discovery would call into question the interest of treatments based on monoclonal antibodies, recently approved, according to them.
- The team is continuing its work on the path of modifying Aβ42 levels to combat Alzheimer’s disease.
In the US, monoclonal antibody drugs designed to clear amyloid from the brain have been approved after being shown to reduce cognitive decline. Looking at the results, Dr Alberto Espay of the University of Cincinnati and his team noticed that these drugs were unintentionally increasing levels of the brain protein Aβ42.
“Amyloid plaques do not cause Alzheimer’s disease, but if the brain produces too much of it to defend itself against infections, toxins or biological changes, it cannot produce enough Aβ42, causing its levels to drop below a critical threshold.”explains the director of the study in a press release. “That’s when the symptoms of dementia appear.”
Faced with this observation, the researchers wanted to see the effect of an increase in the protein in patients suffering from the neurodegenerative disease. And it seems that this helps to slow down cognitive decline.
Brain: Higher levels of brain proteins linked to slower decline
To see if raising Aβ42 levels could be another way to fight Alzheimer’s, the scientists analyzed data from nearly 26,000 patients in 24 randomized clinical trials of these new antibody treatments, assessing cognitive impairment and differences in Aβ42 levels before and after treatment. They found that higher Aβ42 levels after treatment were independently associated with slower cognitive impairment and clinical decline.
“Every story has two sides, even the one we’ve been telling ourselves about how anti-amyloid treatments work: they reduce amyloid.”says Dr. Espay. “In fact, they also increase Aβ42 levels. Even if it’s not intentional, that’s 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 increasing Aβ42 as by decreasing amyloid.”
Alzheimer’s: exploring the Aβ42 levels pathway
For the researcher, the results of his study, published in the journal Brainquestion the value of recently approved monoclonal antibodies that remove amyloid in fighting Alzheimer’s disease. He says removing amyloid from the brain with antibody treatment can be toxic and cause the brain to shrink more quickly. “Should we give patients anti-protein therapy to increase their protein levels? I think the end: increasing Aβ42, does not justify the means: decreasing amyloid.”says Dr. Espay.
The expert believes that it would be better to directly increase Aβ42 levels without targeting amyloid. He is continuing research in this direction.
