Cerebrospinal fluid profiles in Parkinson's disease: No accumulation of glucosylceramide, but significant downregulation of active complement C5 fragment

Yoshiki Niimi, Yasuaki Mizutani, Hisako Akiyama, Hirohisa Watanabe, Ryoichi Shiroki, Yoshio Hirabayashi, Kiyotaka Hoshinaga, Tatsuro Mutoh

研究成果: Article査読

3 被引用数 (Scopus)

抄録

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

本文言語English
ページ(範囲)221-232
ページ数12
ジャーナルJournal of Parkinson's Disease
11
1
DOI
出版ステータスPublished - 2021

All Science Journal Classification (ASJC) codes

  • 臨床神経学
  • 細胞および分子神経科学

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