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Immunological responses may contribute to disease progression and clinical heterogeneity in neurodegenerative dementia, for example, Alzheimer’s disease (AD) and Creutzfeldt-Jakob disease (CJD). Recently, a rapidly progressive form of AD (rpAD) has been described. On neuropathological grounds classical AD and rpAD are not distinguishable at present. All those protein aggregopathies show a state of chronic inflammation with microglia activation and production of proinflammatory cytokines. In this context, it is hypothesized that the severity of the surrounding inflammation substantially contributes to disease progression and accelerated disease courses as seen in rpAD. Using a cytokine multiplex array based on Luminex Technology, we studied 17 pro- and anti-inflammatory cytokines in cerebrospinal fluid (CSF) and serum from patients with classical dementia (AD) or rapidly progressive dementia (Creutzfeldt-Jakob disease (CJD), rpAD). For controls, we chose patients with multiple sclerosis (MS) and non-neurodegenerative diseases. We found a significant and isolated elevation of proinflammatory cytokines (IL-13, TNF-α and G-CSF) in the serum of rpAD patients. In CSF, IL-8 and MCP-1 chemokines were significantly elevated in CJD patients and MCP-1 in AD patients. In conclusion, we found a characteristic proinflammatory cytokine response in the serum of rpAD patients. It might explain the more rapidly progressive course of the rpAD subform and can be helpful in distinguishing between classical AD and rpAD. Electronic supplementary material The online version of this article (doi:10.1186/s12974-014-0170-y) contains supplementary material, which is available to authorized users.