Progress of research into COVID-19 and Parkinson’s disease

ParkinsonNederland visited BPRC for an update on research into brain changes after SARS-CoV-2 infection and their possible link to Parkinson’s disease.

Can a viral infection contribute to changes in the brain that play a role in Parkinson’s disease? BPRC is investigating what happens in the brain for up to a year after a SARS-CoV-2 infection (COVID-19). Initial analyses mainly show changes in brain tissue, cerebrospinal fluid and blood that may be related to processes also seen in Parkinson’s disease.

Recently, the Neurobiology and Ageing team presented the progress of the research to visitors from ParkinsonNederland. “We mainly want to understand what happens in the longer term after an infection,” says Jinte Middeldorp, head of the Neurobiology and Ageing department. “The key question now is whether we still see these kinds of changes twelve months after an infection.”

First indications in blood and brain

The initial results show several changes. Seven weeks and one year after infection, the researchers observed structures in the brain that indicate protein accumulation. They also saw a clear increase in neurofilament light (NfL) in the blood two weeks after infection. NfL is a protein that can be released when nerve cells are damaged. The researchers also observed an increase in the cerebrospinal fluid. Whether levels subsequently decrease again or remain elevated for longer varies between animals.

Using another technique, proteomics, the researchers examine large numbers of proteins simultaneously. In an initial analysis, they looked at 120 proteins associated with disorders of the central nervous system. This panel has now been expanded to 220 proteins, providing broader coverage of disease-related, homeostatic and functional proteins of the central nervous system. The panel also includes additional biomarkers for Parkinson’s disease, including PARK7 and alpha-synuclein (SNCA).

The researchers have access to samples from before the infection and from several time points ranging from two weeks to twelve months afterwards. This allows them to track how changes develop over time. Ultimately, they want to compare the findings in blood and cerebrospinal fluid with what they actually observe in brain tissue. In this way, they are investigating whether biomarkers can be identified that may provide information about changes in the brain.

Existing material provides new insights

An important part of the project is the use of material and data already available at BPRC. BPRC stores brain tissue, blood plasma and cerebrospinal fluid, among other materials, in its biobank. By carrying out different analyses on material from the same animals, researchers can connect an increasing amount of data. Material is also shared with national and international research groups.

This makes it possible, for example, to investigate why changes are more pronounced in one individual than in another. The researchers can link data on brain tissue to factors including viral load, immune responses and routine health checks. “A single blood sample at one point in time tells you much less than being able to see whether a change is still present a month later,” Middeldorp explains.

Next steps in the research

ParkinsonNederland provides financial support for the project and follows its scientific progress throughout its duration. During the visit, the discussion therefore focused not only on the initial results, but also on the next steps. The researchers plan to investigate different brain regions in a more targeted way. They can also compare material from vaccinated and unvaccinated animals to determine whether certain changes differ between the two groups.

There is also interest in the gut and the so-called body-first hypothesis. This hypothesis proposes that, in some patients, the first disease processes may begin outside the brain, for example in the gut.

Jinte Middeldorp believes it is important to involve organisations and patients from the Parkinson’s community in the research. “Patients who have taken a deeper interest in research are often particularly interested in fundamental research. They understand that it may not directly benefit them personally, but that it can offer hope for the future and for the next generation.”