Immune responses in rapidly progressive dementia: a comparative study of neuroinflammatory markers in Creutzfeldt-Jakob disease, Alzheimer's disease and multiple sclerosis

Katharina Stoeck, Matthias Schmitz, Elisabeth Ebert, Christian Schmidt, Inga Zerr

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 rapid form of AD (rpAD) has been described. On neuropathological grounds classical AD and rpAD are not distinguishable at present. All those protein aggregopathies present with 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 rapid dementia (Creutzfeldt-Jakob disease (CJD), rpAD). For controls, we chose patients with multiple sclerosis (MS) and non-neurodegenerative disease controls. We found a significant and isolated elevation of proinflammatory cytokines (IL-13, TNF-¿ and G-CSF) in the serum of rpAD patients compared to disease controls. In CSF, IL-8 and MCP chemokines were significantly elevated in CJD and AD (MCP-1).In conclusion, we found a characteristic proinflammatory cytokine response in the serum of rpAD patients. It might explain the more rapid course of the rpAD subform and can be helpful in distinguishing between classical AD and rpAD.