prm-PASEF-Based Quantification and Isomeric Model for Extended Coverage of Human Plasma Lipidome in Parkinson’s Disease

This study introduces a clinical lipidomics platform
leveraging
fragment-based quantification on parallel reaction monitoring (PRM)-parallel
accumulation serial fragmentation (PASEF) for lipid quantification.
An isomeric model, termed “SN regression model”, built
on specific PASEF-fragment ion patterns, was developed for the quantification
of coeluting sn positional isomers without prior derivatization. This
PASEF-isomeric lipidomics aids in the resolution and quantification
of 176 lipid isomers coeluting in chromatography and/or ion mobility
dimensions, expanding the lipidome quantitative coverage to 481 plasma
lipids covering 14 lipid subclasses with CV <40% for 32 plasma
replicates. We demonstrated the method’s advantage for clinical
research by detailed quantitative lipidomic phenotyping of patients
with Parkinson’s disease, enabling the delineation of new biochemical
pathways affected by the disorder and stratification of patients.
The method’s amenability for high-throughput deep quantitative
coverage of highly structurally resolved lipidome has implications
for improving the diagnosis and understanding of the distinct metabolic
alterations in Parkinson’s disease subgroups and, generally,
for disorders associated with lipid dysregulation.