Magic™ Anti-Tau (Phospho S199) monoclonal antibody, clone FQS3512Z

Background Alzheimer's disease (AD) is characterized by progressive memory loss and cognitive impairment. The aggregation of amyloid beta (A beta) and hyperphosphorylated tau protein are two major pathological features of AD. Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, NOX) has been indicated in A beta pathology; however, whether and how it affects tau pathology are not yet clear. Methods The role of NOX2 in cognitive function, amyloid plaque formation, and tau hyperphosphorylation were examined in APP/PS1 transgenic mice mated with p47(phox)-deficient mice (with deletion of the gene of neutrophil cytosolic factor 1, Ncf1) and/or in p47(phox)-deficient mice receiving intracerebroventricular (ICV) injection of streptozotocin (STZ). The cognitive and non-cognitive functions in these mice were assessed by Morris water maze, Rotarod test, open field, and elevated plus maze. A beta levels, amyloid plaques, p47(phox) expression, and astrocyte activation were evaluated using immunofluorescence staining, ELISA, and/or Western blotting. Cultured primary neuronal cells were treated with okadaic acid or conditioned media (CM) from high glucose-stimulated primary astrocytes. The alteration in tau pathology was determined using Western blotting and immunofluorescence staining. Results Deletion of the gene coding for p47(phox), the organizer subunit of NOX2, significantly attenuated cognitive impairment and tau pathology in these mice. p47(phox) deficiency decreased the activation of astrocytes but had no effect on A beta levels and amyloid plaque formation in the brains of aged APP/PS1 mice, which displayed markedly increased expression of p47(phox) in neurons and astrocytes. Cell culture studies found that neuronal p47(phox) deletion attenuated okadaic acid-induced tau hyperphosphorylation at specific sites in primary cultures of neurons. CM from high glucose-treated WT astrocytes increased tau hyperphosphorylation in primary neurons, whereas this effect was absent from p47(phox)-deficient astrocytes. Conclusions These results suggest that p47(phox) is associated with cognitive function and tau pathology in AD. p47(phox) expressed in neurons contributes to tau hyperphosphorylation directly, while p47(phox) in astrocytes affect tau hyperphosphorylation by activating astrocytes indirectly. Our results provide new insights into the role of NOX2 in AD and indicate that targeted inhibition of p47(phox) may be a new strategy for the treatment of AD.

An ideal on N is a family of subsets of N closed under the operations of taking finite unions and subsets of its elements. The I-open sets of topological spaces, which are determined by an ideal I on N and the topology of the spaces, are a basic concept of ideal topological spaces. However, it encounters some difficulties in the study of certain structures and mappings of topological spaces. In this paper, we discuss some properties of ideal topological spaces based on I-sn-open sets, study the problem generating new topological spaces from ideals, characterize the mappings preserving I-convergence and structure special I-quotient spaces. The following main results are obtained. (i) A mapping f : X -> Y preserves I-convergence if and only if provided U is an I-sn-open subset of Y, then f(-1)(U) is an I-sn-open subset of X. (ii) A topological space X is an I-neighborhood space if and only if every I-continuous mapping on the space X preserves I-convergence. (iii) Suppose that both X, Y are topological spaces and f : X -> Y is a surjective mapping. Then the topology mu of the space Y is the finest topology that makes f preserve I-convergence if and only if mu = tau(f,Isn), if and only if f is an I-sn-quotient mapping and mu = mu(Isn). (iv) Let X be an I-neighborhood space and f : X -> Y be a surjective mapping. Then the topology mu of the space Y is the finest topology that makes f be I-continuous if and only if mu = t(f,I), if and only if f is an I-quotient mapping and Y is an I-sequential space. These show the unique role of I-neighborhood spaces in the study of ideal topological spaces and present a version using the notion of ideals.