Inflammatory and Pro-resolving Mediators in Frontotemporal Dementia and Alzheimer's Disease.

Chronic inflammation contributes to neuronal death in Alzheimer's disease (AD) and frontotemporal dementia (FTD). Here we evaluated inflammatory and pro-resolving mediators in AD and behavioural variant of FTD (bvFTD) patients compared with controls, since neuroinflamamtion is a common feature in both diseases. Ninety-eight subjects were included in this study, divided into AD (n = 32), bvFTD (n = 30), and control (n = 36) groups. The levels of hsCRP, IL-1ß, IL-6, TNF, and TGF-ß1, as well as annexin A1 (AnxA1) and lipoxin A4 (LXA4) were measured in blood and cerebrospinal fluid (CSF). The expression profile of AnxA1 was evaluated in peripheral blood mononuclear cells (PBMCs) as well the distribution of ANXA1 rs2611228 polymorphism. We found reduced peripheral levels of hsCRP and TNF in AD compared with bvFTD patients and controls, and increased levels of TGF-ß1 in AD compared to controls. Moreover, reduced plasma levels of AnxA1 were observed in bvFTD compared to AD and controls. There was a significant cleavage of AnxA1 in PBMCs in both dementia groups. The results suggest differential regulation of inflammatory and pro-resolving mediators in bvFTD and AD, while AnxA1 cleavage may impair pro-resolving mechanisms in both groups.

Resolution of inflammation in neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of neuroinflammatory disorders associated with autoimmune antibodies against aquaporin-4 (AQP4). Accumulating evidence suggests that inflammation is involved in NMOSD pathogenesis. Resolution of inflammation, which is a highly regulated process mediated by specialized pro-resolving lipid mediators (SPMs) is important to prevent over-responsive inflammation. Deficiency in resolution of inflammation may lead to or accelerates inflammatory diseases. However, whether resolution of inflammation is impaired in NMOSD is not known. The objective of this study was to analyze the levels of SPMs in the serum and cerebrospinal fluid (CSF) of NMOSD patients, and to explore the roles of SPMs in clinical features of NMOSD. METHODS: Thirty-five patients with NMOSD, 34 patients with multiple sclerosis, and 36 patients with non-inflammatory neurological diseases were enrolled in this study. Pro-resolving mediators including Annexin A1 (ANXA1) and resolvin D1 (RvD1), as well as pro-inflammatory lipid mediator leukotriene B4 (LTB4) levels were analyzed by enzyme-linked immunosorbent assay. Pro- and anti-inflammatory cytokines as well as chemokine levels were analyzed using cytometric beads array (CBA). RESULTS: Our results showed RvD1 levels were significantly decreased, whereas LTB4 levels were significantly increased in the CSF of NMOSD patients. AQP4-IgG titer was negatively correlated with RvD1 levels in the CSF of NMOSD patients. CONCLUSIONS: Decreased RvD1 levels indicate impaired resolution of inflammation in NMOSD patients. AQP4-IgG may contribute to increased inflammation and lead to unresolved inflammation in NMOSD.

Annexin-1 is no useful surrogate marker of multiple sclerosis - an immunocytochemical study of the cerebrospinal fluid.

OBJECTIVE: Annexin-1 is a calcium-binding protein with anti-inflammatory properties, which has previously been described in MS plaque tissue. We investigated the feasibility and specificity of annexin-1-immuncytochemistry of CSF cells to test its potential as a surrogate marker for MS. MATERIALS AND METHODS: CSF-specimens of 49 MS cases with different courses and 94 control cases were immunocytochemically studied with a monoclonal antibody to annexin-1. RESULTS: The highest level of cytoplasmic immunoreaction was seen in the most acute inflammatory disorders, such as bacterial meningitis and neuroborreliosis. CIS-, RR-MS-, and viral meningoencephalitis cases came next. The lowest annexin-1 expression was observed in neurosyphilis and SP-MS. In PP-MS and non-inflammatory control cases, annexin-1 expression was entirely lacking. CONCLUSION: Immunocytochemical staining of CSF cells with an antibody to annexin-1 is feasible. This may be helpful in further study of its role in the pathophysiology of inflammatory CNS diseases. The expression pattern seems to rather reflect the acuteness of the inflammatory process than specifying a certain underlying pathology. Although differences were observed between diverse disease groups, because of considerable overlap, a certain diagnosis of an individual case cannot be achieved. Thus, at present, we cannot recommend annexin-1 as a reliable surrogate marker of MS.