A new study reveals a protein that helps make an early diagnosis of Alzheimer’s much easier. Scientists found that abnormal blood levels of many proteins could signal the development of dementia up to five years before diagnosis. Before these findings, most of these proteins did not connect to either dementia or Alzheimer’s. Researchers at the Johns Hopkins Bloomberg School of Public Health led the study.
Researchers analyzed blood samples of over 10,000 middle-aged and older adults for the study. The scientists took the samples and stored them for previous large-scale studies decades earlier. The scientists found that abnormal blood levels of 38 proteins increased the risk of developing Alzheimer’s within five years. Among the 38 proteins, 16 seemed to result in an early diagnosis of Alzheimer’s, up to two decades in advance.
The researchers point out that many of the risk markers may occur due to slow cognitive decline from Alzheimer’s. However, they found that high levels of one protein, SVEP1, likely directly contribute to the disease process. The findings were published in the journal Nature Aging on May 14, 2021.
“This is the most comprehensive analysis of its kind to date, and it sheds light on multiple biological pathways that are connected to Alzheimer’s. Some of these proteins we uncovered are just indicators that disease might occur, but a subset may be causally relevant, which is exciting because it raises the possibility of targeting these proteins with future treatments.” -Senior author Josef Coresh, MD, PhD, MHS, George W. Comstock Professor in the Department of Epidemiology at the Bloomberg School.
Currently, over six million Americans live with an Alzheimer’s Disease diagnosis. It’s the most common form of dementia, which results in cognitive and physical decline. Researchers have searched for a cure for decades, but to date, no treatments exist to slow or stop the disease.
How specific proteins could help with early diagnosis of Alzheimer’s
Scientists say that making an early diagnosis of Alzheimer’s gives patients the best outlook. Treating Alzheimer’s before dementia symptoms begin developing could stop the disease altogether. Thus far, scientists have focused on two major Alzheimer’s brain pathology features to evaluate patients’ risk.
Amyloid-beta proteins known as plaques and tau protein have been the focus of scientists researching Alzheimer’s risk. Brain imaging of plaques and blood or cerebrospinal fluid levels of amyloid-beta or tau have been able to predict Alzheimer’s well in advance.
However, scientists have noticed a significant flaw in this method of diagnosing Alzheimer’s. Humans have thousands of other vital proteins in their cells and blood. In recent years, scientists have made many advancements in measuring these proteins from blood samples. For this study, researchers wanted to analyze whether these techniques could also help make an early diagnosis of Alzheimer’s.
The study about proteins linked to Alzheimer’s disease
The scientists analyzed blood samples of over 4,800 late-middle-aged participants in the Atherosclerosis Risk in Communities (ARIC) research. Since 1985, researchers have run a large epidemiological study of heart disease-related risk factors and outcomes in four U.S. communities.
A laboratory technology company called SomaLogic collaborated on the study. Using a recently developed technology, SomaScan, they recorded blood levels of almost 5,000 distinct proteins in the ARIC samples. After analyzing the results, the team discovered that abnormal levels of 38 proteins led to a higher risk of Alzheimer’s within five years.
Next, they used SomaScan to measure protein levels from over 11,000 blood samples from younger ARIC volunteers from 1993-95. They found that, of the 38 proteins, 16 were linked to an early diagnosis of Alzheimer’s within two decades.
Essential proteins linked to early diagnosis of Alzheimer’s
To validate these findings, scientists analyzed results from a different patient population. They studied effects from a previous SomaScan of blood samples taken from Icelanders from 2002-06. That study also evaluated proteins, including 13 of the 16 identified in the ARIC analyses. Among those 13 proteins analyzed, researchers linked six to an increased Alzheimer’s risk over a 10-year follow-up period.
In another analysis, scientists compared those proteins with data from past investigations into the genetic factors contributing to Alzheimer’s. They determined that the SVEP1 protein didn’t just increase the likelihood of an early Alzheimer’s diagnosis. Instead, it triggered the disease.
While scientists don’t yet fully understand how SVEP1 functions, some studies have linked it to other diseases. This year, a study found that the protein was a risk marker for atherosclerosis, which causes heart attacks and strokes.
Other proteins which could help make an early diagnosis of Alzheimer’s include several essential immune proteins. This reiterates previous findings over several decades which have found an association between Alzheimer’s and immune overactivity in the brain.
Researchers will continue using SomaScan and other similar techniques to study proteins in blood samples from long-term studies. They hope to identify potential pathways that trigger Alzheimer’s to improve treatments for the devastating disease. They’ve also studied how protein levels in the ARIC samples can predict other conditions, like vascular disease in the brain, kidneys, and heart.