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.