Abstract: The invention provides methods and composition developed to be used with imaging techniques and useful for diagnosis and monitoring the pain generator(s) of axial pain with or without radiculopathy and methods for screening therapeutic compounds potentially useful for treating axial pain with or without radiculopathy. Alternatively, degenerated discs can be monitored and treated before occurrence of a pathological pain condition. Pain markers and markers of degeneration include markers of neuronal, vascular, immune and matrix elements.

Abstract: In one or a plurality of embodiments, there is provided a target molecule of amylospheroid, which is expressed in mature neurons and to which the amylospheroid binds to induce death of cells. Further, in one or a plurality of embodiments, there is provided a method and a substance for inhibiting death of mature neurons induced by the amylospheroid. In one aspect, the present disclosure relates to a use of Na+/K+-ATPase ?3 as a binding target molecule of amylospheroid. In another aspect, the present disclosure relates to a method for suppressing death of mature neurons induced by the amylospheroid, including inhibiting protein-protein interaction between the amylospheroid and the Na+/K+-ATPase ?3, and the like.

Abstract: A cyclic peptide or a salt thereof of formula (1): X-Leu-Val-Y1-Y2 (1), where X is Lys, Arg, His, Ala, Gly, Ser, or Thr; and Y1 and Y2, which are identical to or different from each other, each represent a group represented by formula (2): where Ar1 represents an aromatic hydrocarbon group or an aromatic heterocyclic group; R1 represents a hydrogen atom, an alkyl group, a cycloalkyl group, a haloalkyl group, an aromatic hydrocarbon group, or an aromatic heterocyclic group; and n is an integer from 0 to 2. In the cyclic peptide has an ?-amino group at the amino terminus of the amino acid sequence which is linked, via a peptide bond, to the carboxyl group at the carboxyl terminus of the amino acid sequence.

Abstract: The present invention relates to anti-PHF-tau antibodies and methods of making and using them.

Abstract: The compound (2R,2?R)-bis(((((tetrahydro-2H-pyran-4-yl)oxy)carbonyl)oxy)methyl) 1,1?-adipoylbis(pyrrolidine-2-carboxylate) possesses physicochemical properties suitable for pharmaceutical development and is capable of generating (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC) in quantities capable of depleting serum amyloid P component (SAP) efficiently following oral administration, making it useful in the treatment of amyloidosis, Alzheimer's disease, type 2 diabetes mellitus and osteoarthritis.

Abstract: In sporadic Alzheimer's disease, neurofibrillary lesion formation is preceded by extensive post-translational modification of the microtubule associated protein tau. Immunoassays have been developed recently that detect tau in biological specimens, thus providing a means for pre-mortem diagnosis of Alzheimer's disease, which has remained elusive. These assays have been improved by the analysis of relevant post-translational modifications, such as phosphorylation, however opportunity for improvement remains. The present invention addresses this issue by disclosing synthetic methylated peptides derived from the tau protein of paired helical filaments and non-diseased control brain. Alzheimer's disease specificity is provided by the presence or absence of methyl moieties on lysine residues and differences between mono-, di-, and tri-methylation.

Abstract: Provided herein is a method of bioassay for the quantification of peptide fragments relevant to neurodegenerative conditions. The method comprises cleaving a Tau protein by a secretase, such as ADAM10, to form a neo-epitope. The method comprises contacting a blood derived sample with an antibody specific for the neo-epitope and determining the level of binding of the antibody to peptide fragments comprising the neo-epitope in the sample. Neo-epitope containing peptide levels are found to be inversely correlated to cognitive function.

Abstract: The invention relates to means for detecting, binding, removing and/or neutralizing agonistic antibodies associated with dementia, preferably Alzheimer's disease or vascular dementia.

Abstract: The present invention relates to the field of biomarkers. More specifically, the present invention relates to assay reagents useful in detecting neurogranin. In a specific embodiment, the present invention provides an isolated antibody or fragment thereof that specifically binds to neurogranin. In another embodiment, the present invention provides a polynucleotide aptamer that specifically binds neurogranin.

Abstract: Methods for preventing and/or treating symptoms of Post-Traumatic Stress Disorder (PTSD) are provided. The preferred method comprises administration of an effective amount of insulin to the upper one-third of a mammal's, preferably a human, nasal cavity, thereby enabling the administered at least one effective amount of insulin to bypass the patient's blood-brain barrier and be directly delivered to the patient's CNS. Another embodiment comprises utilizing vasoconstrictors to enhance targeting of an effective amount of insulin to the CNS while reducing non-target exposure.

Abstract: The invention is based, at least in part, on the finding that a dimeric version of a BBB-transmigrating antibody (e.g., the TMEM30A (CDC-50A) binding antibody, FC5) was found to greatly enhance transport across the BBB as compared to monovalent FC5 VHH. The invention provides, inter alia, molecules that increase transport of pharmacologically active agents across the blood brain barrier, methods for increasing transport across the blood brain barrier, and methods of treatment of disorders or diseases having a neurological component.

Abstract: The invention provides anti-human alpha-synuclein antibodies and methods of using the same.

Abstract: The present invention provides oligopeptides, in particular, Ang-(1-7) derivatives, and methods for using and producing the same. In one particular embodiment, oligopeptides of the invention have higher blood-brain barrier penetration and/or in vivo half-life compared to the native Ang-(1-7), thereby allowing oligopeptides of the invention to be used in a wide variety of clinical applications including in treatment of cognitive dysfunction and/of impairment.

Abstract: The present invention provides methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with neurofibrillary tangles. In particular, the invention relates to humanized antibodies, which specifically recognize and bind to phosphorylated pathological protein tau-conformers to methods and compositions involving said antibodies for the therapeutic and diagnostic use in the treatment of tauopathies including Alzheimer's Disease (AD).

Abstract: The invention relates to antibodies, antibody fragments and binding agents that specifically recognize oligomeric tau but do not bind to monomelic tau, fibrillar tau or non-disease associated forms of tau.

Abstract: The invention provides methods and kits for detecting conformationally altered proteins and prions in a sample. In one embodiment, the conformationally altered proteins and prions are associated with amyloidogenic diseases.

Abstract: The invention provides methods of treatment or prophylaxis of damaging effects of penetrative injury to the brain or other part of the central nervous system. The methods are based in part on results in a rodent model of penetrative ballistic injury showing that an inhibitor of PDF-95 NMDAR interaction is effective in inhibiting neurological deficits resulting from such injury. The methods are useful for treating subjects having or at risk of penetrative brain injury, including subjects who have been shot in the head or at risk of such injury (e.g., military or law enforcement personnel).

Abstract: This application discloses a BBB-selective antibody. The BBB-selective antibody comprises a protein encoded by a DNA sequence comprising SEQ ID NO:7 (CDRH1 of scFv 15), SEQ ID NO:8 (CDRH2 of scFv 15), SEQ ID NO:9 (CDRH3 of scFv 15), SEQ ID NO:10 (CDRL1 of scFv 15), SEQ ID NO:11 (CDRL2 of scFv 15) and SEQ ID NO:12 (CDRL3 of scFv 15) or a DNA sequence comprising SEQ ID NO:19 (CDRH1 of scFv 38), SEQ ID NO:20 (CDRH2 of scFv 38), SEQ ID NO:21 (CDRH3 of scFv 38), SEQ ID NO:22 (CDRL1 of scFv 38), SEQ ID NO:23 (CDRL2 of scFv 38) and SEQ ID NO:24 (CDRL3 of scFv 38). Preferably, the BBB-selective antibody comprises a protein encoded by SEQ ID NO:1 or 3.

Abstract: The present invention relates to Protoxin-II variants, polynucleotides encoding them, and methods of making and using the foregoing.

Abstract: This disclosure relates to diagnostic testing for subjects with or at risk of dementia and methods related thereto. In certain embodiments, the disclosure relates to methods of diagnosing a frontotemporal lobar degeneration subtype comprising measuring total Tau and Tau phosphorylated at threonine 181 in a sample from a subject, calculating a ratio of Tau phosphorylated at threonine 181 to total Tau, and making a diagnosis of the subtype based on said ratios. Typically, the sample is of cerebrospinal fluid and the frontotemporal lobar degeneration subtypes are selected from frontotemporal lobar degeneration with immunoreactive lesions to Tau and frontotemporal lobar degeneration with immunoreactive lesions to TAR DNA binding protein of 43 kD.