Objective: To explore piperine as a potential biomarker for Parkinson’s disease (PD) among GBA and LRRK2 mutation carriers and non-carriers.

Background: Piperine is a yellow crystalline alkaloid originally isolated from Piper nigrum. It is known to have both anti-inflammatory and antioxidant properties and to correlate strongly with dietary black pepper consumption. Preclinical models have shown a neuroprotective potential of piperine; however, the association with PD remains unclear.

Method: Plasma samples were obtained from 640 subjects in the Parkinson’s Progression Markers Initiative (PPMI) who differed by disease status (PD or healthy control [HC]) and genotype (pathogenic GBA or LRRK2 variant or neither) but were matched for age, sex, and (among PD cases) disease duration and levodopa usage. Samples were analyzed by HPLC and LC-MS. Analytes and normalized analyte ratios (n=330, including piperine and piperine/curcumin ratio to correct for dietary spice intake) were analyzed using ANCOVA with terms for PD status, genotype, levodopa use, and their interactions, adjusting for age and sex. Associated nominal and Benjamini-Yekutieli (BY) corrected p-values are reported.

Results: PD participants have a 32% lower piperine level compared to HC (p=0.0007; BY-corrected p=0.22) and a 36% lower piperine/curcumin ratio (p=0.0001; BY-corrected p=0.032). The piperine/curcumin ratio was lower in PD vs. HC regardless of genetic status (GBA+ -45%, p=0.01; LRRK2+ PD -32%, p=0.04; GBA-/LRRK- PD -31%, p=0.04; BY-corrected p=1.00 for all).

Conclusion: Both piperine and the ratio of piperine/curcumin may contribute to a plasma biomarker distinguishing PD+ from PD-, irrespective of genetic status. The lower piperine and piperine/curcumin ratio in PD may be due to aversion to black pepper ingestion, altered pharmacokinetics of piperine, or a potential neuroprotective effect in PD. These findings warrant further epidemiological and clinical study, as well as laboratory investigation of potential neuroprotective mechanisms of piperine in preclinical models.

(Acknowledgments: Expert and collaborative contributions were provided by Sarah Huntwork-Rodriguez, Romeo Maciuca, and Jung Suh of Denali Therapeutics. This study is funded by the Michael J Fox Foundation for Parkinson’s Research, Aligning Science Across Parkinson’s (ASAP), and NIH R01NS110879.)

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lower-plasma-piperine-levels-in-parkinsons-disease-a-ppmi-metabolomics-analysis/