Sphingomyelin as a myelin biomarker in CSF of acquired demyelinating neuropathies

Abstract

Fast, accurate and reliable methods to quantify the amount of myelin still lack, both in humans and experimental models. The overall objective of the present study was to demonstrate that sphingomyelin (SM) in the cerebrospinal fluid (CSF) of patients affected by demyelinating neuropathies is a myelin biomarker. We found that SM levels mirror both peripheral myelination during development and small myelin rearrangements in experimental models. As in acquired demyelinating peripheral neuropathies myelin breakdown occurs, SM amount in the CSF of these patients might detect the myelin loss. Indeed, quantification of SM in 262 neurological patients showed a significant increase in patients with peripheral demyelination (p = 3.81 * 10 − 8) compared to subjects affected by non-demyelinating disorders. Interestingly, SM alone was able to distinguish demyelinating from axonal neuropathies and differs from the principal CSF indexes, confirming the novelty of this potential CSF index. In conclusion, SM is a specific and sensitive biomarker to monitor myelin pathology in the CSF of peripheral neuropathies. Most importantly, SM assay is simple, fast, inexpensive, and promising to be used in clinical practice and drug development.

White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease

“…We have previously shown CSF levels of soluble TREM2 to be increased in the prodromal at-risk state of Alzheimer’s disease ( Suarez-Calvet et al , 2016 b ), preceding the estimated age of onset of dementia symptoms by ∼5–10 years as estimated in autosomal-dominant Alzheimer’s disease ( Suarez-Calvet et al , 2016 a ). Although it remains largely unclear which ligands bind to the TREM2 receptor, recent in vivo experiments in mice suggest that sphingomyelin stemming from damaged myelin ( Capodivento et al , 2017 ) binds to the TREM2 receptor, entailing the activation of microglia ( Wang et al , 2015 ). Thus, in Alzheimer’s disease higher fibre tract damage may result in increased number of microglia and/or higher microglia activity via the TREM2 receptor.…”

Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging

“…Sphingomyelin is a major component of peripheral nerve myelin, where it represents 10–35% of the total lipids in mice (Garbay, Heape, Sargueil, & Cassagne, ). Degradation of sphingomyelin is reported following peripheral nerve injury (Patti et al, ) and chemotherapy‐induced peripheral neuropathy (Stockstill et al, ); and sphingomyelin content of myelinating DRG cultures correlates with state of demyelination following forskolin treatment (Capodivento et al, ). Triacylglycerides are lipids with very short half‐lives used primarily for energy production or storage.…”

Monocarboxylate transporter 1 in Schwann cells is critical for maintenance of sensory nerve myelination during aging

“…Degradation of sphingomyelin is reported following peripheral nerve injury (Patti et al, 2012) and chemotherapy-induced peripheral neuropathy (Stockstill et al, 2018); and sphingomyelin content of myelinating DRG cultures correlates with state of demyelination following forskolin treatment (Capodivento et al, 2017). Triacylglycerides are lipids with very short half-lives used primarily for energy production or storage.…”