Low Cerebrospinal Fluid Sulfatide Predicts Progression of White Matter Lesions – The LADIS Study

Abstract

Background/Aims: Demyelination and axonal degeneration are the hallmarks of established white matter lesions (WML). The neurochemistry of ongoing WML is only partially known. We explored cerebrospinal fluid (CSF) substances as markers of brain tissue damage in relation to progression of WML rated on magnetic resonance imaging. Methods: CSF from elderly individuals with WML was analyzed for amyloid markers, total τ, hyperphosphorylated τ, neurofilament protein light subunit, sulfatide and CSF/serum-albumin ratio. After 3 years, a follow-up magnetic resonance imaging was performed. Progression of WML was rated using the Rotterdam Progression Scale (RPS). Results: 37 subjects (age 73.6 ± 4.6 years) were included. Subjects with more pronounced progression (RPS > 2; n = 15) had lower mean sulfatide concentration at baseline as compared to subjects with no or minimal progression (RPS 0–2; n = 22) according to univariate analyses (p = 0.009). Sulfatide was the only biomarker that predicted the RPS score according to regression analysis, explaining 18.9% of the total variance (r = 0.38, p = 0.015). Conclusion: The correlation of CSF sulfatide levels and RPS scores may reflect a remyelination response to the demyelination process associated with WML. Furthermore, the results strengthen the notion that WML pathology is different from that of Alzheimer’s disease.

The Pathobiology of Vascular Dementia

“…Attempts to remyelinate are present in the damaged white matter in leukoaraiosis (Jonsson et al, 2012). Oligodendrocytes are responsible for the formation and maintenance of the myelin sheet.…”

The impact of cerebrovascular aging on vascular cognitive impairment and dementia

“…In damaged WM, there may be compensatory attempts to remyelinate axons, but most of these efforts fail (Franklin and Ffrench-Constant, 2008; Jonsson et al, 2012). The following factors are responsible for this failure: 1) Oligodendrocytes and OPCs are extremely vulnerable to hypoxia and oxidative stress in ischemic WM (Back et al, 2011; Fernando et al, 2006) (French et al, 2009); 2) withdrawal of trophic support from endothelial cells reduces remyelination capacity (Arai and Lo, 2009); 3) failure of OPC maturation prevents myelination.…”

Phospholipids and Alzheimer’s Disease: Alterations, Mechanisms and Potential Biomarkers

“…Sulfatide brain levels were not reduced in dementia with Lewy bodies and were elevated in different brain regions of individuals with Parkinson’s disease [40]. CSF sulfatide levels in individuals with vascular dementia were elevated compared to controls and individuals with AD [41], and low CSF sulfatide levels could predict progression of white matter lesions [42]. However, specificity and sensitivity of sulfatide as a potential biomarker of AD has yet to be determined.…”