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

Abstract

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 materialThe online version of this article (doi:10.1186/s12974-014-0170-y) contains supplementary material, which is available to authorized users.

Plasma total prion protein as a potential biomarker for neurodegenerative dementia: diagnostic accuracy in the spectrum of prion diseases

“…CSF 14‐3‐3 was analysed as described before . For detection of a prion disease‐associated mutation and assessment of codon 129 polymorphism in PRNP , genetic testing was performed as described before .…”

Proteomic differences in amyloid plaques in rapidly progressive and sporadic Alzheimer’s disease

“…Research examining rpAD is limited; however the amyloid plaque and neurofibrillary tangle morphology and distribution, as well as CSF levels of total tau, phosphorylated tau, Aβ40 and Aβ42 are similar to sAD[18, 68]. Distinctions with sAD include a younger average age at onset, a low frequency of the APOE e4 allele, a higher proportion of patients having 14-3-3 in the CSF, and increased serum levels of specific pro-inflammatory cytokines (IL-6, IL-13, TNFα, G-CSF)[18, 68, 75]. Depending on how rpAD is defined, its frequency is estimated at ~10% of all AD cases[17].…”

Cytokine profiles and the role of cellular prion protein in patients with vascular dementia and vascular encephalopathy

“…Therefore, the importance of inflammation in the pathogenesis 285 is still debated. Several studies report that inflammatory mechanisms may be involved in the 286 development of cognitive decline and the pathophysiology of brain(Stoeck et al, 2014). In 287 the present study, we investigated the expression of a panel of pro-and anti-inflammatory 288 cytokines as well as three chemokines in the serum and CSF samples of patients with VD and 289 VE.…”