Cerebrospinal Fluid Sulfatide Levels Lack Diagnostic Utility in the Subcortical Small Vessel Type of Dementia

Article type: Research Article

Authors: Svensson, Johan^{a; *} | Blomqvist, Maria^{b; c} | Kettunen, Petronella^d | Eckerström, Carl^{d; e} | Henricsson, Marcus^f | Jonsson, Michael^d | Bjerke, Maria^{g; h} | Månsson, Jan-Eric^{b; c} | Wallin, Anders^d

Affiliations: [a] Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden | [b] Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden | [c] Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden | [d] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden | [e] Department of Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg. Sweden | [f] Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden | [g] Laboratory of Neurochemistry, Department of Clinical Biology and Center for Neurosciences, UZ Brussel and Vrije Universiteit Brussel, Brussels, Belgium | [h] Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium

Correspondence: [*] Correspondence to: Dr. Johan Svensson, Department of Internal Medicine, Gröna Stråket 8, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. Tel.: +46317411712; Fax: +4631821524; E-mail: johan.svensson@medic.gu.se.

Abstract: Background:Sulfatides (STs) in cerebrospinal fluid (CSF), as well as magnetic resonance imaging (MRI)-detected white matter hyperintensities (WMHs), may reflect demyelination. Here, we investigated the diagnostic utility of CSF ST levels in the subcortical small vessel type of dementia (SSVD), which is characterized by the presence of brain WMHs. Objective:To study the diagnostic utility of CSF ST levels in SSVD. Methods:This was a mono-center, cross-sectional study of SSVD (n = 16), Alzheimer’s disease (n = 40), mixed dementia (n = 27), and healthy controls (n = 33). Totally, 20 ST species were measured in CSF by liquid chromatography-mass spectrometry (LC-MS/MS). Results:CSF total ST levels, as well as CSF levels of hydroxylated and nonhydroxylated ST species, did not differ across the study groups. In contrast, CSF neurofilament light chain (NFL) levels separated the patient groups from the controls. CSF total ST level correlated with CSF/serum albumin ratio in the total study population (r = 0.64, p < 0.001) and in all individual study groups. Furthermore, CSF total ST level correlated positively with MRI-estimated WMH volume in the total study population (r = 0.30, p < 0.05), but it did not correlate with CSF NFL level. Conclusion:Although there was some relation between CSF total ST level and WMH volume, CSF ST levels were unaltered in all dementia groups compared to the controls. This suggests that CSF total ST level is a poor biomarker of demyelination in SSVD. Further studies are needed to investigate the mechanisms underlying the marked correlation between CSF total ST level and CSF/serum albumin ratio.

Keywords: Alzheimer’s disease, cerebrospinal fluid, mixed dementia, sulfatide species, sulfatides, subcortical small vessel type of dementia, white matter hyperintensities

DOI: 10.3233/JAD-201552

Journal: Journal of Alzheimer's Disease, vol. 82, no. 2, pp. 781-790, 2021