Key Points:
- New research links decreased proteins, not amyloid plaques, to Alzheimer’s disease.
- The study found that individuals already accumulating plaques in their brains who are able to generate high levels of soluble amyloid-beta have a lower risk of evolving into dementia over a three-year span.
- Researchers envision a future with two approaches to treating neurodegenerative diseases: rescue medicine and precision medicine.
New research from the University of Cincinnati supports the hypothesis that Alzheimer’s disease is caused by a decline in levels of a specific protein—not by amyloid plaque buildup as was thought for the last century or so.
The study centers around a protein called amyloid-beta. The protein normally carries out its functions in the brain in a form that is soluble, but it sometimes hardens into clumps, known as amyloid plaques. Study author Alberto Espay, MD, and his colleagues hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing. These levels decrease because the normal protein, under situations of biological, metabolic or infectious stress, transform into the abnormal amyloid plaques.
Previous research from the team found that regardless of the buildup of plaques in the brain, people with high levels of soluble amyloid-beta were cognitively normal, while those with low levels of the protein were more likely to have cognitive impairment.
In the current study, the team analyzed the levels of amyloid-beta in a subset of patients with mutations that predict an overexpression of amyloid plaques in the brain, which is thought to make them more likely to develop Alzheimer’s disease. But even in this group of patients, the researchers found similar results as the study of the general population.
“What we found was that individuals already accumulating plaques in their brains who are able to generate high levels of soluble amyloid-beta have a lower risk of evolving into dementia over a three-year span,” said Espay.
The research found that with a baseline level of soluble amyloid-beta in the brain above 270 picograms per milliliter, people can remain cognitively normal regardless of the amount of amyloid plaques in their brains.
The research is moving forward to study if increasing the levels of soluble amyloid-beta in the brain is a beneficial therapy for patients with Alzheimer’s. Espay said it will be important to ensure that the elevated levels of the protein introduced into the brain do not then turn into amyloid plaques, since the soluble version of the protein is needed for normal function to make an impact in the brain.
On a larger scale, the researchers said they believe a similar hypothesis of what causes neurodegeneration can be applied to other diseases, including Parkinson’s and Creutzfeldt-Jakob disease, with research ongoing in these areas as well.
Information provided by University of Cincinnati.