Increased intrathecal inflammatory activity in frontotemporal dementia: pathophysiological implications

OBJECTIVE: Immunological mechanisms may be part of the pathophysiological mechanisms in frontotemporal dementia (FTD), but hitherto only vague evidence of such mechanisms has been presented. The aim of this study was to compare the cerebrospinal fluid (CSF) levels of the pro-inflammatory cytokines interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha, and the anti-inflammatory cytokine transforming growth factor (TGF)-beta in patients with FTD and normal controls. Furthermore, serum levels of TNF-alpha, TGF-beta, and IL-1beta were measured in FTD patients.

METHODS: The CSF levels of IL-1beta, TNFalpha, and TGF-beta were measured using ELISA in 19 patients with FTD and 24 sex and age matched healthy controls.

RESULTS: The CSF levels of TNF-alpha (FTD 0.6 pg/mL (median: lower, upper quartile 0.3, 0.7); controls: 0.0 pg/mL (0.0, 0.0); p = 0.008) and TGF-beta (FTD 266 pg/mL (157, 371), controls: 147 pg/mL (119, 156); p = 0.0001) were significantly increased in FTD patients compared with controls. No correlations were found between CSF and serum levels of the cytokines. In the controls, but not in the FTD patients, a positive correlation was found between the CSF levels of TGF-beta and age (r = 0.42, p < 0.05). No correlation was found between any of the cytokines and degree of brain atrophy or white matter changes. No differences between the groups were found for age, gender, or CSF/serum albumin ratio.

CONCLUSIONS: The results suggest an increased intrathecal production of both pro- and anti-inflammatory cytokines in FTD. As no correlations were found with the albumin ratio, and no correlations between CSF and serum levels of the cytokines were found, these changes in the CSF cannot be explained by a systemic overproduction of cytokines.