Hexosylceramides as intrathecal markers of worsening disability in multiple sclerosis.
Checa A, Khademi M, Sar DG, Haeggström JZ, Lundberg JO, Piehl F, Olsson T, Wheelock CE.
Mult Scler. 2014 . pii: 1352458514561908. [Epub ahead of print]
BACKGROUND:Sphingolipids are important components of neurons and the myelin sheath whose levels are altered in multiple sclerosis (MS).
OBJECTIVES:We aimed to determine if cerebrospinal fluid (CSF) sphingolipids can be used as markers of MS disease progression.
METHODS: We analysed sphingolipids in CSF from 134 individuals. The MS group included 65 patients divided into 41 relapsing-remitting MS (RRMS) and 24 progressive MS (ProgMS). In addition, a group of 13 early MS/clinically isolated syndrome (EarlyMS) and two control groups consisting of 38 individuals with other neurological diseases (OND) and 18 OND with signs of inflammation (iOND) were analysed. A follow-up study included 17 additional RRMS patients sampled at two time points 4.7±1.7 years apart.
RESULTS: Levels of sphingomyelin (SM)- and hexosylceramide (HexCer)-derived sphingolipids increased in the CSF of patients with MS independently of the fatty acid chain length in RRMS (p<0.05). Levels of palmitic acid (16:0)-containing HexCer (HexCer16:0) increased significantly in ProgMS compared with the OND (p<0.001), iOND (p<0.05) and EarlyMS (p<0.01) groups and correlated with Expanded Disability Status Scale in RRMS in both studies (p=0.048; p=0.027).
CONCLUSION:HexCer16:0 is a promising candidate marker of disease progression in MS, especially in RRMS.
Electronmicrograph of whorls of myelin sheath wrapping around an axon
The 16-carbon fatty acid palmitic acid (HexCer 16:0) and other lipids are major components of myelin and form compact, highly organized membrane structures which is important for its role as an electrical insulator of axons. It is therefore not surprising that myelin injury leads to release of fatty acids into the surrounding cerebrospinal fluid, where it is readily measurable. Here the authors demonstrate that release of HexCer 16:0 is a factor associated with progression in MS, in the same way release of neurofilaments from axons is predictive of progression. In another words demyelination causes disability.
Unfortunately, dietary ingestion of fatty acids does not lead to their replacement or incorporation into the brain. Although, subcutaneous injection in mice seems to do the trick!
Labels: HexCer 16:0, Progression