Objective: Frontotemporal dementia (FTD) is one of the most common forms of primary degenerative dementia. The etiology of FTD is in most cases unknown although mutations in the tau-gene on chromosome 17 has been described in hereditary FTD. In order to increase the knowledge of the underlying pathophysiological mechanisms of FTD, we investigated the cerebrospinal fluid (CSF) levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1b), and transforming growth factor-beta (TGF-beta).
Design: First clinical diagnosis of FTD was made with help from results of an extensive neuropsychiatric investigation including medical history, standard blood chemistry, neuropsychiatric status, neuropsychology, MRI of the brain, EEG, CBF investigation with SPECT. Lumbar puncture to collect CSF was done in a standardized way. Controls were investigated in a similar mode. Then CSF samples were sent to the neurochemical laboratory for further analyses. Clinical diagnosis and biochemical analyses were performed blindly from each other.
Materials and Methods: The CSF levels of IL-1b, TNF-alpha and TGF-beta were measured using sandwich ELISA in 19 patients with FTD and 24 age-matched healthy controls. Diagnosis of FTD was made according to the updated Consensus criteria for frontotemporal lobar dementia (Lund-Manchester Reseacrh Criteria). Controls were all healthy volunteers. The control group was matched to the FTD group for age and gender.
Results: The CSF-levels of TNF-alpha (FTD: 0,5±0.3 pg/mL, vs Controls: 0.2±0.4 pg/mL, mean±SD; p=0.008) and the CSF-TGF-beta (FTD: 269±119 pg/mL, vs Controls: 136±42 pg/mL, mean±SD; p=0.0001) were significantly increased in FTD compared to controls. No significant difference was found for CSF-IL-1b. In FTD, a positive correlation was found between the CSF-TNF-alpha and age (r=0.62). In controls, a positive correlation was found between age and CSF-TGF-beta (r=0.42). No differences between the groups were found for age, gender or CSF/Serum albumin ratio.
Conclusion: The results suggest increased production of anti-inflammatory cytokines (TGF-beta) in FTD and possibly also proinflammatory cytokines (TNF-alpha). Since no correlations were found to albumin ration, the increase of cytokines in CSF suggests an intrathecal inflammation in FTD.
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