Scientists have found hundreds of changes in the blood that may help explain why some people develop memory and thinking problems linked to Alzheimer’s disease.
The findings suggest that the disease may involve much more than changes happening inside the brain.
Alzheimer’s is the most common cause of dementia. It slowly damages memory, thinking and the ability to manage everyday life, and the risk rises sharply with age.
For many years, researchers have focused heavily on amyloid, a substance that can build up into sticky plaques in the brain. These plaques are an important sign of Alzheimer’s, but they do not explain every case or why people with similar brain changes can have very different symptoms.
Researchers at Emory University’s Goizueta Brain Health Institute and partner organizations wanted to look more widely at what might be happening throughout the body. They studied blood samples from 2,139 people taking part in four major research groups.
The team measured more than 6,000 different proteins in the blood. Proteins carry out many jobs in the body, from fighting infection and producing energy to repairing tissue and removing damaged material.
The scientists then compared these blood changes with signs of Alzheimer’s in the brain and with participants’ memory and thinking abilities. They also looked at other types of brain damage that often appear alongside Alzheimer’s.
The results showed that many blood proteins were connected with memory and thinking. Some were involved in the immune system, energy production, the removal and recycling of damaged material, and the structures that support and surround cells.
Importantly, amyloid did not explain all of these connections. Even after researchers took amyloid into account, many blood proteins were still linked with thinking ability.
In one part of the study, researchers had detailed information from brain examinations after death. Known forms of brain damage explained only about half of the blood proteins linked with thinking ability.
This raises an intriguing possibility. Processes happening elsewhere in the body may influence brain health and could affect how quickly memory and thinking decline.
That does not mean scientists have proved that these blood changes cause Alzheimer’s. Some changes may be a result of the disease, while others could reflect aging, other illnesses or the body’s response to damage.
Still, the findings could broaden the search for new treatments. If certain processes outside the brain contribute to Alzheimer’s, future medicines might be able to target those processes without needing to act directly inside the brain.
The research could also help scientists improve blood tests for Alzheimer’s. Blood tests are easier and less invasive than spinal fluid tests, and they could eventually help doctors identify disease-related changes earlier or follow how a person’s condition changes over time.
However, a single simple blood test based on these newly identified proteins is not ready for routine use. The researchers said more studies are needed to understand which changes are most useful for predicting disease and which might become treatment targets.
The study included participants from the Bio-Hermes study, the Emory Goizueta Alzheimer’s Disease Research Center, other Emory research studies, and the Religious Orders Study and Rush Memory and Aging Project. Using several large groups helped the researchers check whether important findings appeared across different sets of people.
The research was published online in the journal Nature Aging on September 10, 2025. It was led by researchers including Erik C. B. Johnson, Allan I. Levey and colleagues at Emory and partner institutions.
Overall, the study adds to growing evidence that Alzheimer’s is a complex disease involving many parts of the body. Looking beyond amyloid and beyond the brain itself may give scientists new ways to understand, detect and eventually treat the disease.
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