Abstract Details

Title No Accumulation of Glucosylceramide in PD Cerebrospinal Fluid

Topic Movement Disorders

Presentation(s) P14 - Poster Session 14 (11:45 AM-12:45 PM)

Poster/Presentation
Number 5-001

Objective We investigated whether glucosylceramide accumulation and abnormal immune status in the brain are associated with PD

Background As mutations in glucocerebrosidase 1 (GBA1) are a major risk factor for Parkinson’s disease (PD), decreased GBA1 activity might play an important role in the pathogenesis of the disease. However, there are currently no reports on glucosylceramide levels in the cerebrospinal fluid (CSF) from PD.

Design/Methods We measured glucosylceramide by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) as well as levels of the active fragment of complement C5, C5a, in the CSF of 33 PD, 15 amyotrophic lateral sclerosis (ALS) and 22 neurologically normal control (NNC) subjects. Serum C5a levels in all PD and ALS cases and in a limited number of NNC subjects (n = 8) were also measured.

Results C5a levels in CSF were significantly downregulated in PD compared with NNC. Moreover, CSF C5a/serum C5a ratio showed pronounced perturbations in PD and ALS patients. LC-ESI-MS/MS revealed a statistically significant accumulation of a specific subspecies of glucosylceramide (d18 : 1/C23 : 0 acyl chain fatty acid) in ALS, but not in PD. Interestingly, CSF glucosylceramide (d18 : 1/C23 : 0) exhibited a significant correlation with CSF C5a levels in PD, but not ALS. No correlation was observed between C5a levels or glucosylceramide subspecies content and disease duration, levodopa equivalent daily dose or Hoehn & Yahr staging in PD.

Conclusions Our findings demonstrate complement dysregulation without glucosylceramide accumulation in PD CSF. Furthermore, we found an association between a specific glucosylceramide subspecies and immune status in PD.

Authors/Disclosures
Tatsuro M. Mutoh, MD, PhD, FAAN (Fujita Health University Hospital) PRESENTER	Dr. Mutoh has nothing to disclose.
Yoshiki Niimi	Yoshiki Niimi has nothing to disclose.
	No disclosure on file
Hirohisa Watanabe, MD, PhD (Fujita Health University)	Dr. Watanabe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda. Dr. Watanabe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Watanabe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Dr. Watanabe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Ono . Dr. Watanabe has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Avvie.
	No disclosure on file

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