Scientists spot 32 proteins that suggest Alzheimer’s risk

By Denise Mann Health Day Reporter

THURSDAY, July 20, 2023 (HealthDay News) — It’s hard to predict in advance who will develop Alzheimer’s disease. Now, a new study suggests that certain markers in the blood may show up 10 to 20 years before symptoms start and could help doctors determine who is at high risk for dementia.

For the study, the researchers analyzed more than 4,800 proteins in the blood of more than 10,000 middle-aged people (ages 45 to 65) over the age of 25. They identified 32 proteins linked to the risk of dementia later in life.

“Biological changes occur outside the brain as early as mid-adulthood in people at risk who develop dementia decades later,” the study author said. Keenan Walker. He is a researcher in the Multimodal Neurodegenerative Disease Imaging Unit (MIND) at the US National Institute on Aging.

“These changes tell us a bit more about the specific biological processes that can go wrong early in people at risk for dementia,” Walker added.

Now the researchers plan to see if they can identify more proteins that may cause brain changes linked to Alzheimer’s disease. “We believe that by identifying causally relevant proteins, we can potentially identify new therapeutic targets,” Walker said.

Although many of these markers were found in the brain, some were associated with tissues outside the brain. For example, markers related to immune system function and biological processes that regulate protein production, function, and health changes occur at least 20 years before the onset of dementia.

“Later in the disease process, proteins involved in the coagulation system and the complement signaling pathway showed signs of dysregulation,” Walker said.

Clotting, or the development of blood clots, has been linked to the risk of Alzheimer’s disease. The complement signaling pathway contains certain proteins that make up the beta-amyloid plaques and tau tangles that are hallmarks of Alzheimer’s disease in the brain.

These are more than just markers in the blood that can predict Alzheimer’s disease risk, Walker said. Age is the biggest risk for dementia, but other factors play a role, including the presence of heart disease.

The new study identifies several proteins that can be found in the blood and may help predict progression to dementia in later life in midlife, said Percy Griffon. He is director of science engagement at the Alzheimer’s Association in Chicago.

“It’s important to develop tools for early detection and accurate diagnosis of Alzheimer’s disease and other dementias before people start showing symptoms,” said Griffin, who was not involved in the study.

No single biomarker can tell that person will develop Alzheimer’s disease or another type of dementia. “By combining multiple biomarkers, we can increase our confidence in a diagnosis,” he said. “While more work and validation is needed, the opportunities found in this document may add to this sequel in the future.”

Dr. Howard Fillit is the co-founder and scientific director of the Alzheimer’s Drug Discovery Foundation in New York. He also reviewed the new study.

This research was made possible by the advent of proteomics, or the large-scale study of proteins. “Using this technology, researchers have analyzed over 4,800 proteins and narrowed their way to a small subset that demonstrates the best prediction for the development of Alzheimer’s disease,” Fillit said. “Years ago we could look at one or two proteins at a time, and now we can look at 4,800, and that’s a scientific feat.”

It’s an exciting time in Alzheimer’s disease research for many reasons, he said.

In early July, the US Food and Drug Administration approved Leqembi (lecanemab), a disease-modifying drug that can slow the progression of Alzheimer’s disease by reducing amyloid plaques that form in the brain.

“Five to 15 years ago, if you said we could get rid of plaque, I’d be amazed, but now we can do it, and it’s amazing,” Fillit said. “If we get rid of the plaques, it looks like we can slow down the disease.”

SOURCES: Keenan Walker, PhD, researcher, Multimodal Neurodegenerative Disease Imaging Unit (MIND), US National Institute on Aging, Baltimore, MD; Percy Griffin, PhD, director, science engagement, Alzheimer’s Association, Chicago; Howard Fillit, MD, co-founder, scientific director, Alzheimer’s Drug Discovery Foundation, New York City; Science Translational MedicineJuly 19, 2023

Copyright © 2023 health day. All rights reserved.