Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer’s Disease with Positron Emission Tomography

Aggregates of tau and beta amyloid (Aβ) plaques constitute the histopathological hallmarks of Alzheimer’s disease and are prominent targets for novel therapeutics as well as for biomarkers for diagnostic in vivo imaging. In recent years much attention has been devoted to the discovery and development of new PET tracers to image tau aggregates in the living human brain. Access to a selective PET tracer to image and quantify tau aggregates represents a unique tool to support the development of any novel therapeutic agent targeting pathological forms of tau. The objective of the study described herein was to identify such a novel radiotracer. As a result of this work, we discovered three novel PET tracers (2-(4-[¹¹C]­methoxyphenyl)­imidazo­[1,2-<i>a</i>]­pyridin-7-amine <b>7</b> ([¹¹C]­RO6924963), <i>N</i>-[¹¹C]­methyl-2-(3-methylphenyl)­imidazo­[1,2-<i>a</i>]­pyrimidin-7-amine <b>8</b> ([¹¹C]­RO6931643), and [¹⁸F]­2-(6-fluoropyridin-3-yl)­pyrrolo­[2,3-<i>b</i>:4,5-<i>c</i>′]­dipyridine <b>9</b> ([¹⁸F]­RO6958948)) with high affinity for tau neurofibrillary tangles, excellent selectivity against Aβ plaques, and appropriate pharmacokinetic and metabolic properties in mice and non-human primates

Modulation of immune responses by targeting CD169/Siglec-1 with the glycan ligand

A fundamental role in the plant-bacterium interaction for Gram-negative phytopathogenic bacteria is played by membrane constituents, such as proteins, lipopoly- or lipooligosaccharides (LPS, LOS) and Capsule Polysaccharides (CPS). In the frame of the understanding the molecular basis of plant bacterium interaction, the Gram-negative bacterium Agrobacterium vitis was selected in this study. It is a phytopathogenic member of the Rhizobiaceae family and it induces the crown gall disease selectively on grapevines (Vitis vinifera). A. vitis wild type strain F2/5, and its mutant in the quorum sensing gene ΔaviR, were studied. The wild type produces biosurfactants; it is considered a model to study surface motility, and it causes necrosis on grapevine roots and HR (Hypersensitive Response) on tobacco. Conversely, the mutant does not show any surface motility and does not produce any surfactant material; additionally, it induces neither necrosis on grape, nor HR on tobacco. Therefore, the two strains were analyzed to shed some light on the QS regulation of LOS structure and the consequent variation, if any, on HR response. LOS from both strains were isolated and characterized: the two LOS structures maintained several common features and differed for few others. With regards to the common patterns, firstly: the Lipid A region was not phosphorylated at C4 of the non reducing glucosamine but glycosylated by an uronic acid (GalA) unit, secondly: a third Kdo and the rare Dha (3-deoxy-lyxo-2-heptulosaric acid) moiety was present. Importantly, the third Kdo and the Dha residues were substituted by rhamnose in a not stoichiometric fashion, giving four different oligosaccharide species. The proportions among these four species, is the key difference between the LOSs from both the two bacteria. LOS from both strains and Lipid A from wild type A. vitis are now examined for their HR potential in tobacco leaves and grapevine roots