antibody against A beta 1-40 epitope 17-21

Objectives - To detect the reactivity pattern of sera from patients with mild and severe Alzheimer's disease (AD) to specific antibodies targeting different epitopes in the primary structure of amyloid-beta (A beta). Materials and methods - Sera from patients diagnosed with mild or severe AD were used. The reactivity of sera to monoclonal antibodies recognizing 1-7, 5-10, 9-14 and 17-21 epitopes of A beta 1-40 at 36-42 degrees C was determined by an enzyme-linked immunosorbent assay. Proteinase K digestion of A beta 1-40 was investigated by dot blotting at 36 and 40 degrees C. Results: - Sera of patients with AD displayed reactivity only with monoclonal antibody recognizing the epitope 17-21 (4G8). The reactivity of sera from patients with severe AD was less than that of sera from patients with mild AD at temperatures 36-41 degrees C, with no difference at 42 degrees C. Patients with severe AD displayed lesser digestion with proteinase K. Conclusions - Sera derived from patients with AD could react with monoclonal antibodies directed to 17-21 sequences of A beta 1-40 in a temperature-dependent manner. The severity of AD is associated with greater A beta 1-40 aggregation and resistance to proteinase K. The present results may be of value in staging and following up of patients with AD

Arthritis

Altered vascular reactivity due to endothelial dysfunction, consequent to vascular damage, is observed in rheumatoid arthritis. We investigated the effect of angiotensin (Ang)-(17) on vasculature changes in arthritis induced by complete Freund's adjuvant in male Wistar rats. Arthritis decreased soluble receptor for advanced glycation end products (sRAGE) whereas elevated aortic RAGE expression, increased interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), systolic blood pressure and the contractility induced by phenylephrine and KCl. Moreover, arthritis decreased the relaxing effect of acetylcholine. Neither arthritis nor Ang-(17) altered sodium nitroprusside relaxation. Ang-(1-7) reversed the effect of arthritis on TNF-alpha, sRAGE and RAGE expression without any effect on the IL-1 beta. Ang-(1-7) decreased phenylephrine and KCl contractility, especially in the endothelial-denuded aorta, whereas increased acetylcholine relaxation in the endothelial-intact aorta. Ang-(1-7) could find its place in the treatment protocol of arthritis and vascular diseases. (C) 2016 S. Karger AG, Base

Serum Following Intraamygdaloid Injection

Amyloid beta-protein (A) assembly into toxic fibrillar structures is seminal in development of senile plaques, the pathological hallmark of Alzheimer's disease. Blocking this process could have a therapeutic value. beta-sheet breaker peptides (beta SBP) decrease A beta fibrillogenesis and neurotoxicity by preventing or dissolving misfolded A beta aggregates. The present study investigated the effects of beta SBPs on A beta 40-related neuropathology, memory impairment in 8-armed radial maze and expression of A beta 40 in brain and serum. A beta 40 was injected into amygdaloid nucleus followed 8 days later by octapeptide beta SBPs 15-22, 16-23 and 17-24. A beta 40 was detected not only in amygdala, but also in serum. A beta 40 induced cellular changes in amygdala and additionally in hippocampus. A beta 40 decreased correct choices, whereas increased errors (both number of arms revisited and total number of revisits) and latency of completing the maze test. The beta SBPs decreased A beta 40-induced pathological changes, memory impairment and A beta 40 expression in serum. The beta SBP15-22 distinctively decreased the total errors on day 14. The present results show that octapeptide beta SBPs corrected A beta 40-induced memory impairment, and support investigation of beta SBPs as a promising treatment of diseases characterized by neurodegeneration and memory impairment such as Alzheimer's disease

Serum Following Intraamygdaloid Injection

Amyloid beta-protein (A) assembly into toxic fibrillar structures is seminal in development of senile plaques, the pathological hallmark of Alzheimer's disease. Blocking this process could have a therapeutic value. beta-sheet breaker peptides (beta SBP) decrease A beta fibrillogenesis and neurotoxicity by preventing or dissolving misfolded A beta aggregates. The present study investigated the effects of beta SBPs on A beta 40-related neuropathology, memory impairment in 8-armed radial maze and expression of A beta 40 in brain and serum. A beta 40 was injected into amygdaloid nucleus followed 8 days later by octapeptide beta SBPs 15-22, 16-23 and 17-24. A beta 40 was detected not only in amygdala, but also in serum. A beta 40 induced cellular changes in amygdala and additionally in hippocampus. A beta 40 decreased correct choices, whereas increased errors (both number of arms revisited and total number of revisits) and latency of completing the maze test. The beta SBPs decreased A beta 40-induced pathological changes, memory impairment and A beta 40 expression in serum. The beta SBP15-22 distinctively decreased the total errors on day 14. The present results show that octapeptide beta SBPs corrected A beta 40-induced memory impairment, and support investigation of beta SBPs as a promising treatment of diseases characterized by neurodegeneration and memory impairment such as Alzheimer's disease

pathways

Interleukin (IL)-6 is an important mediator of neurovascular dysfunction, neurodegeneration and/or neuroinflammation. We previously reported that brain pericytes released higher levels of IL-6 than did glial cells (astrocytes and microglia) in response to tumor necrosis factor (TNF)-alpha. Moreover, pericytes stimulated with TNF-alpha enhanced activation of BV-2 microglia. In this study, we investigated the mechanisms of TNF-alpha mediated induction of IL-6 release from brain pericytes and astrocytes and whether pericyte-derived IL-6 would facilitate activation of BV-2 microglia. Using rat brain pericyte and astrocyte primary cultures and pharmacological inhibitors, we found that, TNF-alpha induced the highest levels of IL-6 release from pericytes by activating the inhibitor kappa B (I kappa beta)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF kappa B) and Janus family of tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT)3 pathways. STAT3 contributed to INF-alpha induced nuclear translocation of phospho-NF kappa B in pericytes. INF-alpha-induced IL-6 release in astrocytes was mediated by NFKB but not by STAT3. The presence of pericytes amplified TNF-alpha-induced iNOS mRNA expression in BV-2 microglia. This effect was blocked by a neutralizing antibody for IL-6. These findings indicated that crosstalk between the I kappa beta-NF kappa B and JAK-STAT3 pathways is a pericyte specific mechanism, not occurring in astrocytes, for TNF-alpha-induced IL-6 release. IL-6 derived from pericytes enhanced microglial activation. Our findings increase understanding of the role of pericyte-microglia crosstalk in the brain under neuroinflammatory conditions and suggest a potentially attractive therapeutic target for brain inflammation. (C) 2018 Elsevier B.V. All rights reserved