Ending Alzheimer’s before it starts

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Sebastiaan Engelborghs is a neurologist specialized in neurodegenerative brain diseases and believes in the potential of early diagnosis for Alzheimer’s disease. Engelborghs teaches neurosciences at the University of Antwerp but his main activities are in the clinical and research domains. At the clinical level, Engelborghs coordinates the Antwerp Mind Clinic, where he is also a medical doctor. In the research field he is active as director of BIODEM, a reference center for biological markers of dementia.

“The research of my group focuses on improved diagnostics for Alzheimer’s disease and related diseases. This means on one hand increasing the accuracy of the diagnosis and on the other hand being able to make the diagnosis as early as possible.”

Alzheimer’s disease is caused by the accumulation of specific proteins in the brain and this already starts 10 to 20 years before the first symptoms are visible.

“This offers huge potential for early diagnosis, treatment and prevention. By detecting these protein aggregates on brain scans or via biochemical markers in the cerebrospinal fluid, we can now diagnose Alzheimer before it becomes symptomatic. Unfortunately, this cannot yet be used in clinical practice, since there is no cure for Alzheimer’s, but in scientific research and clinical trials this is an important tool.”

Searching for marks

By correlating Alzheimer’s disease with specific biochemical molecules, biomarkers, a molecular signature for the disease can be established and used to detect the disease early on.
“The use of biomarkers as a way to detect and track disease progression is an important diagnostic and prognostic tool. As biomarkers are discovered they must be validated through clinical studies. Our research group, for example, is collaborating with the company ADx NeuroSciences to clinically validate the biomarkers that they have developed. These studies often include deceased patients, as Alzheimer’s can only be diagnosed with 100% accuracy after autopsy. When we know for sure that a patient had Alzheimer’s, we can look for biochemical changes that are disease-specific and then use these changes for detection. These clinical studies have already demonstrated the value and usefulness of biomarkers in Alzheimer’s disease diagnosis. We have observed that some biomarkers are already deviant many years before the disease symptoms start to show.”

We are beginning to shift towards using biomarkers for early diagnosis in asymptomatic persons.

If you can’t cure it, slow it down

“Many pharmaceutical companies carry out clinical trials with therapeutics which can potentially slow the accumulation of protein. Within the last 10 years however, many, if not all of these trials failed to significantly slow the disease symptoms. This was probably because medication was administered when patients were already in the dementia stage of Alzheimer’s disease. At this stage, substantial brain damage has already occurred and so further slowing down of the disease has no use.”

Companies are now starting new trials, testing the same and novel therapeutic compounds in patients in the pre-clinical stage of the disease.

“Early results are promising. Since treatment cannot reverse the aggregation of proteins but stops or slows further accumulation, early diagnosis is of the utmost importance.”

The (re)search continues

Early detection of Alzheimer’s is a great achievement with potential for successful medical applications in the near future. However, further improvements still need to be made.
“Current markers cannot predict disease progression. The search is still on for new and better biomarkers. For example, one of the earliest phenomena in Alzheimer’s is the loss of synapses in the brain. This occurs before neuronal cell death and probably is a better measure for disease progression. Neurogranin functions as a biomarker for synaptic loss and has more predictive power. By combining different markers it will be possible to make a more accurate prognosis for each patient.
We also collaborate with Christine Van Broeckhoven’s lab. Her lab is specialized at the molecular biology and genetics of Alzheimer’s disease, where as my lab contributes with a clinical-diagnostic and phenotypical approach. Both sides offer important information and by combining them, we can truly make an in-depth characterization of a patient.”

Photo by Vincent Jauniaux, UAntwerpen