Clues in Blood May Explain Alzheimer’s Beyond Amyloid Plaques

Researchers at Emory Goizueta Brain Health Institute and partner institutions have found new clues in the blood that could help explain why Alzheimer’s disease develops and how it affects memory.

The study, published in Nature Aging, examined blood samples from more than 2,100 individuals across four large research cohorts. Using advanced tools, scientists measured thousands of proteins in the blood and linked them to changes in the brain and thinking ability.

Traditionally, doctors have focused on sticky amyloid plaques in the brain as a hallmark of Alzheimer’s.

But the new research shows that many other processes are also at play. The team found that proteins related to the immune system, protein disposal, energy use, and the body’s support structure (called the extracellular matrix) were tied to memory and thinking problems.

Importantly, not all of these changes could be explained by known Alzheimer’s brain changes, suggesting that factors outside the brain—like processes in blood and other organs—may contribute to the disease.

“Many of the proteins we found in blood are not directly tied to what we see in the brain after death,” says Erik Johnson, MD, PhD, senior author, physician and researcher at Emory’s Goizueta Alzheimer’s Disease Research Center. “This means that what’s happening in the rest of the body could play a role in Alzheimer’s risk and how fast the disease progresses.”

The findings may open the door to new treatments that work by targeting these blood-based pathways, rather than trying to deliver drugs directly into the brain.

“This study advances our understanding of proteins in the blood that change with Alzheimer’s disease,” says Allan Levey, MD, PhD,  executive director of the Goizueta Institute at Emory. “This work is foundational to the development of blood tests for detecting different pathologies that occur in the brain along with amyloid plaques, and for clinical translation.”

The work also supports the idea of using blood tests as an easier, less invasive way to study and track Alzheimer’s disease in the future.

Reference: Afshar S, Dammer EB, Bian S, et al. Plasma proteomic associations with Alzheimer’s disease endophenotypes. Nat Aging. 2025. doi: 10.1038/s43587-025-00965-4

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