How Fatty Molecules Affect Brain in Parkinson’s Focus of Study

The Michael J. Fox Foundation and the Shake It Up Australia Foundation are supporting an international project investigating the role of fatty molecules — called lipids — in the brains of people with Parkinson’s disease.

“There is very little known about the role of changes in lipid metabolism in distinct brain regions in Parkinson’s disease. We know it is important, but we don’t know exactly where in the brain, nor how fast and via what metabolic processes these changes are happening,” Shane Ellis, PhD, an assistant professor at Maastricht University and the project’s lead investigator, said in a press release.

The team will include researchers with the Maastricht MultiModal Molecular Imaging Institute (M4I), Lipidomics Consulting, MOBILion Systems and Merck.

“With the assembled team we can now start to understand and visualise, for the first time, the changes in composition and dynamic metabolism (flux) occurring within different brain regions,” Ellis said.

Funding given this project will help scientists to identify ways in which the metabolism of glycosphingolipids (GSLs) — fat molecules associated with early Parkinson’s onset and its rapid progression, and which accumulate due to GBA1 gene mutations, prevalent in this disease — might be restored. The funding’s amount and length were not released.

“We do not know the breadth of alterations in GSLs and how this contributes to Parkinson’s,” said Kim Ekroos, PhD, CEO and founder of Lipidomics Consulting.

Ellis and his team are focused on lipid analysis and mass spectrometry imaging (MSI), a technique that allows large-scale analysis and visualization of molecules, now being developed and applied at M4I.

Current methods only allow GSLs analysis on whole tissue samples. Researchers here will be looking for modifications that occur in specific brain areas, something previously not possible.

“We will combine MSI with isotope labelling methods that allow us to track the synthesis and breakdown rates of GSLs in different brain regions. As well, we will use high-resolution ion mobility to study how larger, more complex GSLs such as gangliosides are altered in Parkinson’s,” Ellis said.

Researchers will also employ a new ionization method, called laser post-ionisation, or MALDI-2, which is reported to increase imaging sensitivity 100 times compared to previous imaging techniques.

“The imaging methods we will utilise provide cellular-level resolution for tissue imaging experiments, which is absolute state-of-the-art,” Ellis said. “The methods we develop will also have direct application to the many other tissue imaging studies.”