TY - JOUR
T1 - Cerebrospinal fluid profiles in Parkinson's disease
T2 - No accumulation of glucosylceramide, but significant downregulation of active complement C5 fragment
AU - Niimi, Yoshiki
AU - Mizutani, Yasuaki
AU - Akiyama, Hisako
AU - Watanabe, Hirohisa
AU - Shiroki, Ryoichi
AU - Hirabayashi, Yoshio
AU - Hoshinaga, Kiyotaka
AU - Mutoh, Tatsuro
N1 - Funding Information:
We would like to thank Toshiki Maeda, MD, Eri Muto, PhD, and Mitsuko Ide, MAgr, for their excellent technical assistance. We also thank Drs. Shinji Ito, Akihiro Ueda, Koichi Kikuchi, Ryunosuke Nagao, and Seiko Hirota for recruiting patients involved in the present work. This work was partly supported by a JSPS KAKENHI Grant Number JP 16k09685 [Grant-in-Aid for Scientific Research (C)] from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, and Research Grants for Intractable Diseases from the Ministry of Health, Labor, and Welfare of Japan to TM. The present work was also partly supported by a JSPS KAKENHI Grant Number JP17K15608 [Grant-in-Aid for Young Scientists (B)] from MEXT to HA. We thank Barry Patel, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/ac) for editing a draft of this manuscript.
Funding Information:
This work was partly supported by a JSPS KAK-ENHI Grant Number JP 16k09685 [Grant-in-Aid for Scientific Research (C)] from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, and Research Grants for
Publisher Copyright:
© 2021 - IOS Press. All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
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U2 - 10.3233/JPD-202310
DO - 10.3233/JPD-202310
M3 - Article
C2 - 33216044
AN - SCOPUS:85099917127
VL - 11
SP - 221
EP - 232
JO - Journal of Parkinson's Disease
JF - Journal of Parkinson's Disease
SN - 1877-7171
IS - 1
ER -