The aim of this study was to investigate two putative pathophysiological aspects of the common neurodegenerative disorder frontotemporal dementia (FTD). To this end, cerebrospinal fluid (CSF) levels of tau (total tau) and the light subtype of the neurofilament proteins (NFL) were studied in patients with FTD (n=16) and in age-matched controls (n=16). In addition, serum was analysed for IgG and IgM antibodies to the most common gangliosides and sulfatide in FTD patients (n=13) and in age-matched controls (n=20). The CSF-NFL levels were increased in FTD (1606+/-1151 pg/ml, mean+/-S.D.; P<0.001) compared with controls (308+/-203 pg/ml), whereas the CSF-tau levels were normal. In serum, autoantibody IgG-GA1 was significantly increased in FTD (P<0.05) compared with controls. No correlations were found between the effect parameters and demographic variables in any group. The results of this study suggest that cytoskeleton proteins other than tau are also involved in the pathophysiology of FTD and that autoimmunity may be part of the pathophysiological processes in FTD, as it is believed to be in Alzheimer's disease.