Scientists discover biomarkers to identify subcortical small-vessel disease

cognitive diseases
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A research team from the University of Gothenburg has discovered two biomarkers that will make it possible to identify patients with subcortical small-vessel disease.

How do these biomarkers work in diagnosing subcortical small-vessel disease?

Over the past few years, subcortical small-vessel disease has become a common cognitive diagnosis among patients. The two biomarkers that researchers have determined are capable of identifying someone with the disease are measured in spinal fluid and blood – this increases the potential for both treatment and development of medication.

This disease is one of the most common cognitive diseases, as well as Alzheimer’s disease and mixed dementia – this is where Alzheimer’s disease occurs together with vascular damage in the brain.

Petronella Kettunen, lead author, Associate Professor in Neurobiology at the University of Gothenburg, and Project Manager for the Gothenburg Mild Cognitive Impairment study, explained: “Up to now, we have had no markers for subcortical small-vessel disease, which means that the disease could not be easily identified by testing samples of spinal fluid or blood.

“We have now opened up an opportunity to identify the disease, enabling help for this patient group in the form of lifestyle changes and blood pressure-reducing medication.”

How did researchers make this discovery?

Scientists examined several biomarkers and measured them in samples of both spinal fluid as well as blood to determine whether they could be utilised to distinguish between these three common cognitive diseases. A total of 170 patients were included in the study; this number included control subjects. 

What did the results reveal?

The study confirms that a biomarker for vascular injury, based on the ratio of the protein albumin in spinal fluid and blood, was significantly higher in patients with subcortical small-vessel disease. Additionally, the study also revealed a new biomarker – a fragment of the amyloid precursor protein (APP) in spinal fluid – which was lower in patients with subcortical small-vessel disease.

“When we combined the biomarker for vascular injury with the protein fragment we identified, the potential for separating patients with subcortical small-vessel disease from control subjects, patients with Alzheimer’s disease and patients with mixed dementia was improved,” said Kettunen.

Researchers have noted that their results also improve the possibilities for refining the patient cohorts during clinical trials for new drugs. This means that diagnosing patients with these diseases is important for identifying the correct patient groups for each disease, that in turn, enables future treatment studies.

“For a treatment study for Alzheimer’s disease, for example, you need to know that all of the patients are suffering from Alzheimer’s and not from another cognitive disease. Otherwise, the result will not be accurate,” concluded Kettunen.


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