Abstract Details

Title Peripheral Sphingolipids as Potential Biomarkers of Parkinson disease Including Sex-Related Differences

Topic Movement Disorders

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 5-007

Objective

Objective: Assessment of glucocerebrosidase pathways to better understand the pathophysiology of sphingolipids in Parkinson Disease (PD) associated with a GBA variant (GBAPD), including sex-specific features.

Background Background: Sex-specific differences in both idiopathic PD and GBAPD have been reported. Determining blood-based measures in the glucocerebrosidase pathway, which is perturbed in GBAPD might be useful in understanding these differences.

Design/Methods Methods: Tandem mass spectrometry was utilized to assess levels of targeted sphingolipid substrates and products in 109 GBAPD (62 men, 47 women) and 118 controls (50 men, 68 women) evaluated from four major studies (Mount Sinai (Beth Israel), Parkinson Disease Biomarker Program, Harvard Biomarker Study, BioFIND).

Results Results: GBAPD had elevated hexosylceramides when compared to controls (mean [SD] 652.6 [188.3] pmol/100 μl plasma vs 586.2 [172.8]; p=0.006), while ceramide was reduced compared to controls (498.5 [118.7] vs 530.6 [110.9]; p=0.036). Very long chain ceramides, in particular, were decreased in GBAPD compared to controls (420.16 [101.58] vs 448.53 [98.68]; p=0.034). Levels of hexosylsphingosine were increased in GBAPD compared controls (0.08 [0.04] vs. 0.07 [0.04]; p=0.001). Sex-specific differences in measured levels were found. While Hexosylceramides were increased in GBAPD compared to controls, this increase was driven by women, but not men. Alternatively, while ceramides and were decreased in GBAPD compared to controls, this decrease was driven by men and not by women. Finally, while levels of hexosylsphingosine were increased in GBAPD compared to controls, this difference was driven by GBAPD men compared controls, but not by GBAPD women compared to controls.

Conclusions Conclusion: While there are differences between GBAPD and controls that are detected in plasma, these depend on sex and suggest that men are preferentially shunting from hexosylceramide to hexosylsphingosine whereas women to ceramides. This supports sex-related pathophysiologic differences, and randomization schema for GBA related studies may consider accounting for sex.

Authors/Disclosures
Roberto A. Ortega, MS PRESENTER	Mr. Ortega has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Amanda Glickman	Ms. Glickman has nothing to disclose.
Mariel Pullman, MD (Mount Sinai Beth Israel)	The institution of Dr. Pullman has received research support from Empire Clinical Research Investigator Program.
Clemens R. Scherzer, MD (Yale)	Dr. Scherzer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Scherzer has received research support from NIH. The institution of Dr. Scherzer has received research support from Michael J. Fox Foundation. The institution of Dr. Scherzer has received research support from American Parkinson's Disease Association. Dr. Scherzer has received intellectual property interests from a discovery or technology relating to health care.
Deborah Raymond (Beth Isreal Medical Center)	The institution of Ms. Raymond has received research support from NIH.
	No disclosure on file
Andrea S. Yoo, MD (Weill Cornell Medicine)	Dr. Yoo has nothing to disclose.
William C. Nichols, PhD	No disclosure on file
Dimitri Krainc, MD, PhD (Northwestern University)	Dr. Krainc has nothing to disclose.
Susan B. Bressman, MD, FAAN (Mount Sinai Health System)	The institution of Dr. Bressman has received research support from Michael J Fox Foundation . The institution of Dr. Bressman has received research support from NIH .
	No disclosure on file
	No disclosure on file
	No disclosure on file
Rachel J. Saunders-Pullman, MD (Mount Sinai Beth Israel, Neurology, Downtown Union Square)	The institution of Dr. Saunders-Pullman has received research support from NIH, Bigglesworth Family Foundation, Empire Clinical Research Investigatory Program.

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