Specific Proteins in Blood Samples May Predict Increased Alzheimer’s Risk

A large-scale analysis of blood samples identified 38 proteins associated with an increased risk of developing Alzheimer’s disease within 5 years, according to a study published in Nature Aging. Among the proteins, 16 appeared to predict Alzheimer’s disease risk as many as 20 years in advance.

“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,” said study senior author Josef Coresh, MD, PhD, MHS, a professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. “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.”

The study began with an analysis of blood samples from 4,110 late-middle-age participants in the Atherosclerosis Risk in Communities (ARIC) cohort from four communities in the United States. Researchers used recently developed technology to measure levels of 4,877 plasma proteins in the banked samples, and then compared levels in participants who did not develop Alzheimer’s disease over the next 5 years with levels in 428 participants who did.

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They found 38 proteins whose abnormal levels were significantly linked with a higher risk of developing Alzheimer’s disease in the population, according to the study.

Next, researchers quantified protein levels for more than 11,000 blood samples taken in the 1990s when ARIC study participants were younger.

Abnormal levels of 16 proteins among the previously identified 38 were linked with the development of Alzheimer’s disease nearly 2 decades ahead of time.

When researchers compared the identified proteins with data from previous genetic studies of Alzheimer’s disease, one in particular—SVEP1—appeared not just a marker but an active player in disease development. SVEP1 was just linked with atherosclerosis in a study published earlier this year.

“Pathway analyses for the broader set of dementia-associated proteins implicated immune, lipid, metabolic signaling, and hemostasis pathways in dementia pathogenesis,” researchers said.

—Jolynn Tumolo

References

Walker KA, Chen J, Zhang J, et al. Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk. Nature Aging. 2021;1:473-489.

Researchers identify proteins that predict future dementia, Alzheimer's risk [press release]. Baltimore, Maryland: Johns Hopkins Bloomberg School of Public Health; May 17, 2021.