Objective: To identify novel biomarkers of Parkinson’s disease (PD) in Parkinson’s Progression Markers Initiative (PPMI) cerebrospinal fluid (CSF) samples.
Background: Altered polyamine levels in plasma and CSF have emerged as potential biomarkers for PD diagnosis and progression, but validation in larger cohorts is needed.
Method: CSF from 640 subjects from PPMI who carried a known GBA or LRRK2 PD-pathogenic variant or neither and who were diagnosed with PD or were unaffected controls (UC) were analyzed by liquid chromatography coupled to mass spectrometry. Polyamines (cadaverine, putrescine, spermidine, etc.) were analyzed by ANCOVA, adjusting for relevant covariates, including age, sex, and genotype. Multiplicity corrections were performed using the Benjamini-Yekutieli (BY) method. We also conducted a secondary analysis using CSF metabolomic data from the BIOFIND cohort (https://biofind.loni.usc.edu/).
Results: Polyamines were significantly higher in PD compared to controls: cadaverine (32%), N-acetylputrescine (39%), N-acetylspermidine (19%), and putrescine (22%) (BY-corrected p<0.0001). Trends persisted across genotypes. Sensitivity analyses showed that PD participants on MAO-B inhibitors had significantly higher polyamines (cadaverine by 60%, BY-corrected p<0.0001), while differences were smaller in those without MAO-B inhibitors (cadaverine by 9%; p=0.0031). BIOFIND analysis confirmed the association of elevated N-acetylputrescine and N-acetylcadaverine with MAO-B inhibitor use (both p<0.0001).
Conclusion: Elevated levels of multiple CSF polyamines in PD were largely attributable to the use of MAO-B inhibitors, perhaps reflecting pharmacological inhibition of polyamine metabolism and highlighting the importance of considering PD drug effects when interpreting metabolomic data in PD research. However, residual MAO-B inhibitor-independent elevations of polyamines also suggest their endogenous variation may be linked to PD risk. Further studies are warranted to consider whether polyamines might be useful biomarkers or mediators of PD pathophysiology.
To cite this abstract in AMA style:
N. Xia, R. Maciuca, J. Suh, J. Kluss, S. Davis, R. Bakshi, G. Crotty, A. Ascherio, E. Macklin, S. Huntwork-Rodriguez, M. Schwarzschild. CSF Cadaverine and Other Polyamines as Biomarkers of Parkinson’s Disease: A PPMI Metabolomics Analysis [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/csf-cadaverine-and-other-polyamines-as-biomarkers-of-parkinsons-disease-a-ppmi-metabolomics-analysis/. Accessed October 21, 2026.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/csf-cadaverine-and-other-polyamines-as-biomarkers-of-parkinsons-disease-a-ppmi-metabolomics-analysis/