Dementia is often confused with Alzheimer’s disease, but in reality there are several different brain conditions that can lead to memory loss, confusion, and changes in thinking and behaviour.
One of these conditions is called limbic-predominant age-related TDP-43 encephalopathy, or LATE. This is a recently recognised form of dementia that mainly affects older adults and often appears together with Alzheimer’s disease.
For many years, doctors have only been able to confirm the presence of LATE after a person has died, by studying the brain during an autopsy. There has been no reliable way to diagnose this condition in a living person. This has made it very difficult to understand who has LATE, how it progresses, and how it could be treated.
A new study by Jijing Wang and Hyun-Sik Yang from the Department of Neurology at Mass General Brigham may change that. Their research, published in the journal Molecular Neurodegeneration, explored whether a protein called TDP-43 could be detected in the blood of people who had LATE-related changes in their brain.
TDP-43 is a protein that should normally stay inside brain cells. In people with LATE, however, this protein builds up in an abnormal way, especially in brain areas involved in memory and emotional processing. This build-up leads to damage and loss of nerve cells over time, which then causes memory problems and other symptoms of dementia.
The researchers wanted to know if the same protein that builds up in the brain could also be found in the blood, and whether its levels could act as a sign, or biomarker, of LATE in living people.
To explore this question, they studied blood samples from 50 older adults who had taken part in two long-running research projects: the Religious Orders Study and the Rush Memory and Aging Project in Chicago.
These individuals had donated their brains to science after death, and blood samples had been collected from them several years before they passed away. This made it possible for the researchers to compare the amount of TDP-43 in the blood with the amount of damage seen in the brain later on.
Using an extremely sensitive testing method, the scientists measured both total TDP-43 and a modified version of the protein in the blood samples. They then compared these levels to what they found during the brain examinations after death.
The results were striking. People who had advanced LATE-related brain changes showed much higher amounts of TDP-43 in their blood while they were still alive. This relationship was especially strong in people who also had signs of Alzheimer’s disease in their brains.
Even after the researchers adjusted for other changes linked to Alzheimer’s disease, such as the presence of amyloid plaques and tau tangles, the link between blood TDP-43 and LATE remained strong.
This suggests that the signal from TDP-43 in the blood is not just reflecting Alzheimer’s disease, but is truly tied to the LATE process itself. In simple terms, the blood appeared to be carrying a clear warning sign of what was happening deep inside the brain.
This discovery is important because Alzheimer’s disease can now be detected in living people through blood tests, spinal fluid tests, or specialised brain scans. However, LATE has remained a hidden contributor to dementia because it could only be confirmed through autopsy.
If a reliable blood test for TDP-43 can be developed, doctors may one day be able to tell the difference between Alzheimer’s disease, LATE, or a combination of both while a person is still alive. This would allow for more accurate diagnoses and more personalised treatment plans.
The researchers are cautious but hopeful. They emphasise that this was a small study and that larger, more diverse groups of people need to be studied to confirm the results.
It will also be important to see whether blood levels of TDP-43 change as the disease gets worse, and whether these changes can be used to track the progress of dementia over time. Another important question is whether this blood test will work in people who have LATE but do not have Alzheimer’s disease at the same time.
In reviewing and analysing the findings of this study, it becomes clear that it represents a major step forward in dementia research. By showing that a specific brain protein linked to LATE can be measured in the blood and closely reflects brain damage, the study opens the door to a new way of diagnosing and understanding dementia.
It also highlights that not all memory loss is caused by Alzheimer’s disease alone. Many people may have LATE, either on its own or in combination with Alzheimer’s, and may benefit from different approaches to treatment and care.
Although much more research is needed, this study brings hope that one day a simple blood test could help doctors uncover a hidden cause of dementia, allowing for earlier diagnosis, better planning, and more targeted therapies for millions of people around the world.
If you care about Alzheimer’s disease, please read studies about the protective power of dietary antioxidants against Alzheimer’s, and eating habits linked to higher Alzheimer’s risk.
For more health information, please see recent studies that oral cannabis extract may help reduce Alzheimer’s symptoms, and Vitamin E may help prevent Parkinson’s disease.
The study is published in Molecular Neurodegeneration.
Copyright © 2025 Knowridge Science Report. All rights reserved.
