Header image: Julie van der Zee, VIB-UAntwerp Center for Molecular Neurology
Ten years ago, at age 68, Maria visited the VIB-UAntwerp Center for Molecular Neurology (CMN) for the first time. She and the other volunteers were highly motivated to participate in the research of former CMN Director and dementia research pioneer, Christine Van Broeckhoven. They got a tour of the facility, where researchers explained to them how their blood samples and medical histories would help the team understand dementia.
Now aged 79, Maria is even more enthusiastic about the study. During her follow-up visit, she shares with the nurse Sofie Van de kerckhoven that her motivation to participate has become more personal. She describes how she sometimes forgets names, and has to search for words that once came easily. “My friend has it too,” she tells Sofie. “Is it normal?”
Maria is not alone in her concerns. About 150,000 people in Flanders and Brussels live with dementia today, and it has become one of the most feared health conditions among older adults. The recent European approval of lecanemab — the first disease-modifying therapy for Alzheimer’s — has created a dilemma. The drug works best if administered in the early stages of disease progression, creating a demand for early detection which doctors currently lack the tools to provide.
Image: Nurse Sofie Van de kerckhoven with a study participant.
The Dashboard Warning Light
Alzheimer’s disease begins decades before symptoms appear. VIB scientist Bart De Strooper calls this the “cellular phase” — a long period where the brain mounts a response to the buildup of harmful proteins like amyloid-beta and tau. Eventually these defenses fail — the compensating mechanisms turn pathological and symptoms start to appear.
“My friend has it too. Is it normal?” – Maria, study participant
Doctors currently have two options to detect this pre-symptomatic phase in patients, but both are flawed. PET scans involve radiation and high costs; lumbar punctures require a painful needle inserted into the spine. What doctors need is the equivalent of a dashboard warning light on a car — a simple, reliable signal that catches problems while the brain still seems to be running smoothly.
A Blood-Based Breakthrough
Blood-based biomarkers could be the warning light we need, providing the same information as these invasive procedures with a simple blood draw. The U.S. Food and Drug Administration (FDA) recently approved the first blood test for Alzheimer’s disease, based on the ratio of specific tau and amyloid proteins (pTau217/ß-Amyloid 1-42).
“We need to see the full picture.” – Kristel Sleegers
“The new FDA-approved blood test is a real advance,” says Kristel Sleegers, who leads a research team at the Center for Molecular Neurology. “But it focuses primarily on tau and amyloid-beta. A test measuring one or two proteins captures just a fraction of what’s happening during the decades-long pre-symptomatic period, involving immune responses, metabolic changes, and neuronal dysfunction. We need to see the full picture.”
Sleegers explains that these assays work well in the extremes (for example, identifying those who definitely will or won’t develop dementia), but they leave a large “gray zone”. Doctors cannot use these assays to assess a person who worries about their memory.
Image: Kristel Sleegers, VIB-UAntwerp Center for Molecular Neurology
Taking the Long View on Cognitive Decline
This need for a more precise, non-invasive test is what’s driving the long-term study at the VIB Center for Molecular Neurology. Ten years ago, researchers collected the blood, medical histories, and cognitive score of 1,000 healthy, elderly volunteers. Now, the volunteers have been invited back for the next stage of the study.
“The response has been remarkable,” says Julie van der Zee, who leads the study along with Kristel Sleegers. “Nearly 80 percent of those we’ve contacted have agreed to participate again. We’ve already re-tested more than 200 people. After ten years, at ages ranging from 62 to 93, that level of commitment is extraordinary.”
“Many of the volunteers are motivated by a desire to help science or spare their families the pain of dementia.”
Like Maria, many of the volunteers are motivated by a desire to help science or spare their families the pain of dementia. At her follow-up, Maria gives blood, takes cognitive tests, and even offers a sample of tear fluid. The researchers need these diverse samples because cognitive decline is not a simple disease with a single trajectory. It’s possible for two people to carry the same genetic risk of Alzheimer’s, but for one patient to decline rapidly while the other stays sharp for years.
If cognitive decline varies, then the researchers recognize that the biomarkers must vary too. This understanding has driven a center-wide effort, pooling expertise to investigate multiple biological processes simultaneously in this study, genetic profiles, proteomic profiles, immune responses, etc.
Finding the Tipping Points
A particularly novel angle is the search for extracellular RNA and DNA: genetic fragments floating in blood and tears. Unlike amyloid or tau (which reflect specific protein pathologies), these molecules act as real-time messages from the brain, revealing how cells are changing their gene expression. Remarkably, these traces can be detected using nothing more invasive than a blood draw or a paper strip placed over the eyelid.
Valeriya Malysheva’s lab plans to use causal machine learning algorithms to examine these biomarker patterns and ‘play the film backward’. By tracing biomarker trajectories, the researchers hope to identify specific tipping points — the moments when the brain’s resilience finally gives way. This could tell us not just who needs treatment, but also when. Additionally, it may reveal why some people remain cognitively sharp despite accumulating harmful proteins like amyloid-beta, pointing toward protective mechanisms that enable resilience.
Read this article to learn about Muna Therapeutics’ hopeful solutions for memory loss!
To ensure these discoveries work in the real world, the research team plans to validate their biomarker findings in memory clinics across Belgium. They are also committed to sharing the biomarker data ethically and safely with academic and industry partners, to spark further innovation.
Maria’s Next Visit
“See you in ten years,” Maria tells the nurse, as she finishes her appointment. Contributing to the study gives Maria a sense of purpose, and she leaves the research center with a smile.
In a decade, the landscape may already have progressed far, thanks to studies like this one. The hope is that biomarkers will provide doctors with the precision needed to distinguish between benign forgetfulness and the first sparks of disease. Instead of uncertainty, they could tell patients: “This is just age,” or conversely, ”You were right to worry, but your blood tests caught the disease early, giving us the best possible chance to intervene and protect your future.”
The name Maria has been used in place of a real name to protect the individual’s privacy.
