Pacific northwest bioMedical Innovation Co-Laboratory (PMedIC)

PMedIC Joint Appointee Receives OHSU Paper of the Month Honor

October 31, 2023 | Carolyn Kim

OHSU recently announced that John Melchior's paper entitled "Human cerebrospinal fluid contains diverse lipoprotein subspecies enriched in proteins implicated in central nervous system health" was selected as the paper of the month. Melchior is a PNNL Senior Scientist and holds a joint appointment with OHSU in the Department of Neurology, working with PMedIC. This paper represents important work that will influence future research through PMedIC.

One of the most exciting findings of this study is the diversity of the lipoprotein particles in the cerebrospinal fluid (CSF) and brain. The data indicate that these particles have many functions beyond simple lipid transport and are playing key roles in maintaining brain health. The researchers have unlocked a massive amount of data on these particles, which the researchers have made available to researchers to mine and build upon for making new discoveries. Perhaps more important than that is the demonstration of the power of the developed technology. Using this technology as part of studies analyzing CSF and post-mortem brain tissues of patients with neurodegenerative disease are long overdue and the team has provided a platform and workflow that finally makes this possible. This study is also important as it illustrates the power and impact of collaborative research between PNNL and OHSU in which team members, with complementary expertise are working together to improve cognitive health and to reduce cognitive injury in those impacted by neurological conditions.

Studies on plasma lipoproteins have provided major clues on the pathways that become dysfunctional in cardiovascular disease. Those have led to multiple Nobel Prizes and development of blockbuster drugs like Lipitor that have really helped reduce deaths associated with disease. The team is now unlocking new roles for these particles in diabetes, obesity, heart failure, sepsis, and even pregnancy. The ability to finally obtain similar measures on the brain has equal potential to unlock our understanding of brain pathways that become dysfunctional and lead to neurodegeneration.

The long-term goal is to characterize these particles in different neurological disorders to provide the information needed for development of biomarkers and targeted therapeutics. If the research team can identify populations that protect against specific diseases, the idea would be to find a way to boost those populations to stave off the disease and preserve cognitive function.