Correlation between Intrathecal Sulfatide and TNF-α Levels in Patients with Vascular Dementia

Abstract

Objectives: Subcortical vascular dementia (SVD) is associated with white matter lesions and demyelination. The aim of the present study was to examine the cerebrospinal fluid (CSF) levels of TNF-α, a proinflammatory cytokine mediating myelin damage, in SVD patients. The intrathecal TNF-α levels were related to the clinical symptoms of dementia, as well as to intrathecal levels of sulfatide, a marker of white matter degradation, and of neurofilament, a marker of neuronal degeneration. Methods: CSF levels of TNF-a, sulfatide and neurofilament were all analyzed by immunoenzymatic procedures in 17 patients with SVD and in 26 healthy controls. Results: The intrathecal concentration of TNF-α was significantly increased in SVD patients compared to healthy controls (p = 0.0001). The intrathecal levels of TNF-α were significantly correlated (r = 0.6, p = 0.02) to the levels of sulfatide, but not to the levels of neurofilament, (r = 0.08, NS). Conclusions: We have demonstrated intrathecal production of TNF-α in SVD patients. The correlation between TNF-a and sulfatide levels in the CSF suggests that this apoptosis-inducing cytokine leads to the death of oligodendrocytes, thereby contributing to white matter degeneration, a hallmark of SVD.

The role of apolipoprotein E in lipid metabolism in the central nervous system

“…Whether gradual accumulation of sulfatides in neuronal cells is associated with the pathogenesis of PD remains to be elucidated. Very recently, Tarkowski and colleagues [79] demonstrated alterations in sulfatide mass in CSF of subjects with vascular dementia, suggesting that apoE-mediated sulfatide metabolism might be involved in this disease too. Although available evidence supports the conclusion that sulfatides are only synthesized in oligodendrocytes [64,65], the presence of sulfatides in neurons and astrocytes (e.g.…”

Inflammatory biomarkers are associated with total brain volume

“…Inflammatory cytokines are elevated during acute stroke 1,2 and in the CSF of individuals with subcortical vascular dementia. 3 Furthermore, inflammation is a well-documented feature 4 and purported risk factor 5 for AD. Amyloid deposition stimulates neuroinflammatory processes with neurotoxic effects that exacerbate the pathogenesis of AD and increase neuronal damage.…”

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

“…Fredman et al [15] found significantly elevated CSF sulfatide levels in patients with vascular dementia (n = 20) compared to patients with AD (n = 43) and controls (n = 20). Tarkowski et al [18] studied CSF sulfatide and TNF-α in patients with SVD (n = 17) and healthy controls (n = 26) and found positive correlations in patients with SVD, suggesting that the apoptosis-inducing cytokine leads to the death of oligodendrocytes, thereby contributing to white matter degeneration. Tullberg et al [16] studied WML in patients with normal pressure hydrocephalus (NPH, n = 43) and subcortical arteriosclerotic encephalopathy (SAE, n = 19), respectively, and found that CSF sulfatide levels distinguish between NPH and SAE.…”

“…An elevated CSF/serum albumin ratio has been demonstrated in patients with SVD and WML as a sign of an impaired integrity of the BBB [14]. Sulfatide, a glycosphingolipid enriched in myelin, elevated in CSF in patients with WML, has been regarded as a marker of demyelination [15][16][17][18]. Neurofilament protein light subunit (NFL), a cytoskeletal protein in large myelinated axons, has been found to be significantly increased in patients with SVD [19] and in relation to WML in other clinical forms of dementia [20].…”