Photo courtesy STOCK

Alzheimer’s disease begins changing the brain many years before memory problems become obvious.

Scientists can now detect some of these hidden changes with blood tests, making diagnosis easier than it was in the past.

A new study suggests that measuring a small group of blood proteins together could also help doctors estimate how far the disease has progressed.

Two abnormal proteins are central to Alzheimer’s disease.

The first is amyloid, which can collect between nerve cells and form plaques.

The second is tau, which can build up inside nerve cells and form tangled structures that interfere with normal brain function.

These changes do not happen all at once. Amyloid often begins accumulating first, while widespread tau buildup tends to appear later and is more closely linked to damage to brain cells and worsening symptoms.

Knowing whether a person has reached a more advanced stage of tau buildup can therefore provide important information about the state of the disease.

For many years, Alzheimer’s diagnosis depended heavily on symptoms such as memory loss, confusion, and difficulty with everyday tasks.

By the time these problems become clear, however, biological changes may have been developing for a decade or longer. Researchers have therefore worked to find biomarkers that can detect the disease earlier.

Some of the most useful tests examine cerebrospinal fluid, the liquid surrounding the brain and spinal cord. Another approach uses positron emission tomography, or PET, to create images showing amyloid or tau in the brain.

These methods can provide valuable information, but spinal fluid collection requires a lumbar puncture and PET scans are expensive and not available everywhere.

Blood tests have begun to change this situation. One of the most promising markers is p-tau217, a form of tau protein that can be measured in blood.

Abnormal levels are strongly associated with Alzheimer’s-related changes in the brain and can help identify people who are likely to have amyloid disease.

However, a single blood marker has limits. A test may be good at showing whether Alzheimer’s biology is present but less precise at showing how advanced the disease has become.

This distinction is becoming increasingly important as new treatments and clinical trials target people at particular stages of Alzheimer’s.

Researchers from the University of Gothenburg and collaborating institutions asked whether other blood proteins could add useful information to p-tau217.

They studied large sets of protein measurements from two independent international groups of participants.

The blood-testing technology could measure more than 120 proteins related to inflammation and nerve-cell health from a single sample.

The researchers then used machine learning to search for combinations of proteins that best reflected advanced tau changes in the brain.

Machine learning is a type of computer analysis that can detect patterns across many measurements at once. In this case, it helped the team identify which blood proteins provided useful information beyond p-tau217 alone.

The analysis produced a panel of seven proteins, including p-tau217. When the additional proteins were combined with p-tau217, the blood test was significantly better at identifying people with advanced tau pathology among those who already had elevated amyloid.

It suggests that the wider protein pattern contains information about disease stage that a single marker can miss.

This could have practical value because tau PET imaging is currently one of the best ways to see how far tau has spread through the brain.

If a blood-based protein panel can reliably identify people who have reached a later biological stage, it could reduce the number of patients who need expensive specialized scans.

Blood samples are also easier to collect repeatedly, which could make monitoring more practical.

Better staging may also help with treatment decisions. Alzheimer’s therapies are increasingly designed for particular groups of patients, and the balance between possible benefits and risks may depend on how advanced the disease is.

Doctors need reliable ways to determine who is most likely to benefit from a treatment.

The same approach could make Alzheimer’s clinical trials more efficient.

Researchers often need participants with very specific biological features, such as amyloid buildup combined with a particular amount of tau.

A relatively inexpensive blood test could screen large numbers of people before more costly scans are used to confirm eligibility.

The study was published in JAMA Neurology and involved researchers at the University of Gothenburg and international collaborators.

Guglielmo Di Molfetta, a doctoral student in neurochemistry at the university, said the seven-protein panel could improve the ability of blood testing to recognize a disease profile corresponding to a later stage of Alzheimer’s.

The findings are promising, but they do not mean that PET scans are about to disappear.

Machine-learning models can perform well in research groups yet lose accuracy when applied to people with different ages, health conditions, genetic backgrounds, or stages of disease.

The protein panel will therefore need further testing in large and diverse populations before it can become a routine clinical tool.

Another important question is whether the test can predict what will happen to an individual patient, rather than simply describing the biological stage of disease at one point in time.

Doctors and patients ultimately want to know how quickly memory and thinking may change and whether treatment is altering that course. Longer follow-up studies will be needed to answer those questions.

Overall, the study shows why the next generation of Alzheimer’s blood tests may measure several biological signals rather than relying on one protein.

P-tau217 is already a powerful marker, but combining it with information about inflammation and nerve-cell health may provide a richer picture of what is happening in the brain.

If confirmed, this approach could make advanced Alzheimer’s testing more accessible while helping doctors and researchers use expensive brain scans more selectively.