Plasma ceramide and glucosylceramide metabolism is altered in sporadic Parkinson's disease and associated with cognitive impairment: a pilot study.
BACKGROUND
Mutations in the gene coding for glucocerebrosidase (GBA), which metabolizes glucosylceramide (a monohexosylceramide) into glucose and ceramide, is the most common genetic risk factor for sporadic Parkinson's disease (PD). GBA mutation carriers are more likely to have an earlier age of onset and to develop cognitive impairment and dementia. We hypothesized that plasma levels of lipids involved in ceramide metabolism would also be altered in PD non-GBA mutation carriers and associated with worse cognition.


METHODS
Plasma ceramide, monohexosylceramide, and lactosylceramide levels in 26 cognitively normal PD patients, 26 PD patients with cognitive impairment or dementia, and 5 cognitively normal non-PD controls were determined by LC/ESI/MS/MS.


RESULTS
Levels of all lipid species were higher in PD patients versus controls. Among PD patients, levels of ceramide C16:0, C18:0, C20:0, C22:0, and C24:1 and monohexosylceramide C16:0, C20:0 and C24:0 species were higher (all P<0.05) in those with versus without cognitive impairment.


CONCLUSIONS
These results suggest that plasma ceramide and monohexosylceramide metabolism is altered in PD non-GBA mutation carriers and that higher levels are associated with worse cognition. Additional studies with larger sample sizes, including cognitively normal controls, are needed to confirm these findings.
Departments of Health Science Research and Neurology, Mayo Clinic, Rochester, Minnesota, United States of America.
Michelle M
MM
Mielke
Walter
W
Maetzler
Norman J
NJ
Haughey
Veera V R
VV
Bandaru
Rodolfo
R
Savica
Christian
C
Deuschle
Thomas
T
Gasser
Ann-Kathrin
AK
Hauser
Susanne
S
Gräber-Sultan
Erwin
E
Schleicher
Daniela
D
Berg
Inga
I
Liepelt-Scarfone
D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002518:Ceramides / Q000097:blood*; D002554:Cerebrosides / Q000097:blood*; D003071:Cognition; D003704:Dementia / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics; D006801:Humans; D007790:Lactosylceramides / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D012720:Severity of Illness Index
D015703:Antigens, CD; D015415:Biomarkers; D002518:Ceramides; D002554:Cerebrosides; D007790:Lactosylceramides; C013870:ceramide monohexoside; C009744:CDw17 antigen; D005962:Glucosylceramidase