The pathogenic mechanism underlying the vascular changes in Binswanger's encephalopathy (BE) is unknown. To test whether alterations of the humoral immunity may lead to endothelium damage, we analyzed serum levels of anti-brain endothelium antibodies (ABEA) (IgG and IgM) in 16 BE patients, 19 subjects with ischemic vascular disease without mental deterioration and 18 normal healthy subjects. ABEA IgM were found elevated in 1/16 (6%) BE patients and in 4/19 (21%) patients with cerebrovascular diseases; an increase in ABEA IgG was found in 6/16 (38%) BE patients and in 7/19 (37%) cerebrovascular patients. Association with anti-cardiolipin antibodies (IgG and/or IgM) was found in 50% of BE patients with elevated ABEA and only 10% of those with no increase, whereas high titres of anti-neurofilament antibodies (1:10,000) were detected in 40% and 71% respectively. In BE, ABEA IgG but not IgM showed a trend, although not significant, towards a correlation with the duration of the disease (rs = 0.47; p = 0.07) and significantly correlated with the cognitive function as assessed by the Mini mental state (MMS) score (rs = 0.56; p = 0.02). Higher mean values of the MMS score were found in BE patients with elevated ABEA than in those without (p = 0.04). This difference was not due to language disorders neither to an association with stroke risk factors or anti-neurofilament antibodies. However, there were no significant differences in MMS scores between cerebrovascular patients with ABEA and those without. A "neuro-protective" role is hypothesized for the ABEA in the development of dementia in BE.