New study finds lessening of amyloid-beta may be behind cognitive decline
Although more than 55 million people are living with dementia, scientists still don’t know what causes the most common form, Alzheimer’s. While most experts agree that Alzheimer’s is caused by a build-up of protein amyloid-beta in the brain, new evidence suggests that it’s actually the lessening of amyloid-beta in the brain that’s behind cognitive decline.
The study was published in the September 11, 2024 edition of the journal, Brain.
The Research
A team of researchers from the University of Cincinnati analyzed data from approximately 26,000 participants enrolled in 24 randomized clinical trials for monoclonal antibody treatments. These new treatments, which were approved for treating Alzheimer’s, were chosen based on their ability to increase levels of AB42 in the brain. AB42 is a component of amyloid plaques found in the brains of people with Alzheimer’s.
“AB42 is a protein that reacts to a variety of toxic and infectious exposures in the process of defending the brain,” explains lead author Dr. Alberto Espay, who serves as director and endowed chair of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the UC Gardner Neuroscience Institute, and a neurology professor in the UC College of Medicine. “In that process, AB42 transforms into amyloid plaques and ceases to function. The plaques can be viewed as the tombstones of AB42. I wanted to find out if any cognitive benefits could be explained by the increases in AB42 as much as by the decreases in amyloid plaques.”
According to the scientists, most people with amyloid plaques didn’t develop Alzheimer’s. In fact, by age 85, only 20% of those with amyloid plaques developed the disease.
“We discovered that what keeps people with amyloid plaques cognitively normal is not the level of the plaques in the brain but the extent to which individuals are able to produce enough AB42,” says Espay, “an important protein for brain health, to keep those levels within a normal range.”
Looking at the data
Espay and his team discovered that after the monoclonal antibody treatment, higher levels of AB42 were associated with slower cognitive impairment and clinical decline. It wasn’t surprising, as prior studies had shown something similar—even in those with genetic forms of Alzheimer’s.
As he points out, “Alzheimer’s is a process of loss of AB42, not a gain of amyloid.”
He suggests that medications should aim to increase AB42 directly—not indirectly as the antibodies do.
Future research may include addressing some of the 14 modifiable factors that contribute to at least 45% of all Alzheimer’s cases to see if they can lower plaque loads in the brain while increasing AB42. These modifiable risk factors include:
- Alcohol abuse
- Smoking
- Diabetes
- Obesity
- High blood pressure
- Air pollution
- Brain injury
- Physical inactivity
- Depression
- Social isolation
- Hearing loss
- Lower levels of education
- High cholesterol after age 40
- Vision loss
“Their findings are a sea-change from the currently accepted theory that Alzheimer’s disease is caused by an accumulation of amyloid-beta plaques,” says board-certified neuropsychologist Dr. Karen Sullivan, ABPP, a Reid Healthcare Transformation Fellow at FirstHealth of the Carolinas and owner of I CARE FOR YOUR BRAIN, who was not involved in the study. “The authors are asking us to consider that the complete opposite of this prevailing belief may be true in that increased levels of amyloid-beta results in less cognitive decline.”
MBJ
Wendy Burt-Thomas writes about the brain, mental health and parenting.
Check out the original research:
