Abstract: Genetically modified mice characterized by one or more symptoms or signs associated with expression of human APOE4p and mouse Trem2p and relevant to non-familial late-onset Alzheimer's disease are provided wherein the genome of the mouse includes: 1) a DNA sequence encoding a human APOE4 protein (APOE4p) operably linked to a promoter; and 2) a DNA sequence encoding a mouse Trem2 protein having a mutation p,R47H (Trem2p) operably linked to a promoter, such that the mouse expresses human APOE4p and mouse Trem2p. Methods ace provided for screening for a compound for use in the treatment of Alzheimer's disease using such genetically modified mice.

Abstract: Apparatus (1000) and method for automatically detecting odorant substances based on use of nematodes that includes a mechanical selection unit (100) configured to select nematodes in adult stage from an initial nematode population obtaining an intermediate nematode population, a nematode optical selection unit (200) configured to select from the intermediate population a final population of nematodes in adult stage and to select nematodes in young adult stage from nematodes in egg producing adult stage to be sent to a measurement unit (300) configured to detect the response of nematodes of the final population to a stimulus of an odorant substance, the mechanical selection unit (100) being connected to the optical selection unit (200) by a connection channel with an at least three way branch and the optical selection unit (200) being connected to the measurement unit (300) by a loading microchannel.

Abstract: The present invention is directed to methods for detection, treatment monitoring, and slowing of aging by quantifying miRNAs in bodily fluids.

Abstract: Topical compositions containing lysate of human parthenogenetic stem cells (hpSCs), preferably within a liposomal dispersion, that reduce the visible signs of skin aging and/or cellulite.

Abstract: Disclosed herein are antisense compounds and methods for decreasing alpha-synuclein mRNA and protein expression. Also disclosed herein are methods for treating, preventing, and ameliorating neurodegenerative diseases in an individual in need thereof.

Abstract: Methods and compositions for treating central nervous system diseases and disorders are disclosed.

Abstract: Methods and compositions are provided for modulating Hedgehog (Hh) pathway signaling in a cell. Aspects of the methods include methods for inhibiting Hh pathway-promoted cancer proliferation and/or metastasis that is promoted by Hh pathway signaling, methods for treating cancers promoted by Hh pathway signaling, and methods for screening candidate agents for the ability to treat a cancer promoted by Hh pathway signaling. In addition, reagents and kits thereof that find use in practicing the subject methods are provided.

Abstract: A modified non-human warm-blooded vertebrate animal in which a biologically active human APP polypeptide is expressed, and in which function of its inducible Nitric Oxide Synthase (iNOS) protein is reduced as compared to a non-modified animal, methods of making the animal, and methods of testing a candidate composition for activity in the treatment of Alzheimer's Disease using the animal.

Abstract: A transgenic, non-human animal model for accelerated aging and/or age-related symptom, recombinant nucleic acid molecules, cells and methods that can be used to make such animal model and cells, methods of using the animal model and cells, to descendants of the transgenic non-human animal, obtained by breeding with the same or with another phenotype, and to a cell line or primary cell culture or to an organotypic brain slice culture, derived from the transgenic non-human animal or its descendants are disclosed.

Abstract: The present invention relates to methods and compositions for high content drug screening in C. elegans which may be used to identify compounds that treat disorders associated with protein aggregation.

Abstract: Methods, biomarkers, and expression signatures are disclosed for assessing the disease progression of Alzheimer's disease (AD). In one embodiment, BioAge (biological age), NdStress (neurodegenerative stress), Alz (Alzheimer), and Inflame (inflammation) are used as biomarkers of AD progression. In another aspect, the invention comprises a gene signature for evaluating disease progression. In still another embodiment, methods for evaluating disease progression are provided. In yet another embodiment, the invention can be used to identify animal models for use in the development and evaluation of therapeutics for the treatment of AD.

Abstract: The present invention relates to the fields of knockout (KO) animal production. The invention is directed to a transgenic KO animal comprising a heterozygous or homozygous deletion or functional deletion of the gene's native 3? untranslated region (3?UTR) at least in one of its endogenous gene loci, wherein the disrupted endogenous gene is transcribed into an m RNA without its native 3?UTR. Instead, a 3?UTR of choice, knocked in by the experimenter, is transcribed into an m RNA. The 3?UTR KO animals provide a new approach to study gene function as they enable to overexpress the gene products what are negatively regulated via their 3?UTR-s exclusively in those cells that already transcribe the gene, thereby avoiding the misexpression problem present in the animals produced by conventional transgenesis methods. The invention is further directed to KO animals, in which the gene with deletion of 3?UTR is GDNF, NGF or BDNF.

Abstract: The present invention relates to methods and compositions for high content drug screening in C. elegans which may be used to identify compounds that treat disorders associated with protein aggregation.

Abstract: L-serine, L-serine precursors, L-serine derivatives and L-serine conjugates for treatment, amelioration and/or prevention of protein aggregation/tangles/plaques and diseases associated with protein aggregation/tangles/plaques. In particular, treatments and uses for L-serine, L-serine precursors, L-serine derivatives and L-serine conjugates include Alzheimer's disease (AD), Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Huntington disease (HD).

Abstract: The invention relates to transgenic animals lacking endogenous Ig and capable of producing transgenic antibodies, as well as methods of making the same. The invention further relates to methods for producing transgenic antibodies in such animals, and transgenic antibodies so produced.

Abstract: Methods and compositions relating to Alzheimer's disease are provided, including proteins that are differentially expressed in Alzheimer's disease as compared to the normal state. Further provided are methods, particularly experimental paradigms, for the identification of differential expressed proteins that are potential molecular targets for compounds to treat or prevent Alzheimer's disease. Also provided are methods for the identification and therapeutic use of compounds for the prevention and treatment of Alzheimer's disease.

Abstract: The present invention relates to methods of treatment of clinical disorders associated with protein aggregation comprising administering, to a subject, an effective amount of an anti-protein aggregate (“APA”) compound selected from the group consisting of pimozide, fluphenazine (e.g., fluphenazine hydrochloride), tamoxifen (e.g., tamoxifen citrate), taxol, cantharidin, cantharidic acid, salts thereof and their structurally related compounds. It is based, at least in part, on the discovery that each of the aforelisted compounds were able to promote degradation of aggregated ATZ protein in a Caenorhabditis elegans model system. According to the invention, treatment with one or more of these APA compounds may be used to ameliorate the symptoms and signs of AT deficiency as well as other disorders marked by protein aggregation, including, but not limited to, Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.

Abstract: Evidence indicates dysregulation. of the immunoregulatory molecule CD45 occurs in Alzheimer's disease (AD). Transgenic mice overproducing amyloid-? peptide (A?) and deficient in CD45 (PSAPP/CD45?/?) recapitulate AD neuropathology. Increased cerebral intracellular and extracellular soluble oligomeric and insoluble A?, decreased plasma soluble A? increased microglial neurotoxic cytokines TNF-? and IL-1?, and neuronal loss were found in PSAPP/CD45?/? mice compared with CD45-sufficient PSAPP littermates. After CD45 ablation, in vitro and in vivo studies demonstrate a microglial phenotype whereby microglia phagocytose less A? but display proinflammatory properties. This microglial activation occurs with elevated A? oligomers and neural injury and loss as determined by decreased ratio of anti-apoptotic Bcl-xL to proapoptotic Bax, increased activated caspase-3, mitochondrial dysfunction, and loss of cortical neurons in PSAPP/CD45?/? mice.

Abstract: A biomarker for Alzheimer's disease (AD) comprising a complex of an A? amyloid peptide and a cell or a cellular membrane. Non-invasive methods for diagnosing Alzheimer's disease or monitoring its development or progression using this biomarker.

Abstract: A transgenic animal other than human in which neuropsychiatric disorder condition is developed by the deletion of an HB-EGF gene is obtained. The present invention relates to a transgenic animal other than human in which an HB-EGF gene is deficient and neuropsychiatric disorder condition is developed, and a production method thereof, and a method for screening a therapeutic agent for neuropsychiatric disorder. As a transgenic animal in accordance with the present invention, a transgenic animal in which an HB-EGF gene is specifically deficient in the spiny neurons (striatum, and hippocampus) can be obtained by crossbreeding a transgenic animal that contains a genotype of Gng7(+/cre), and a transgenic animal that contains a genotype of Hb-egf(flox/flox).

Abstract: A transgenic fly whose genome is modified to express enhanced levels of glutamate-cysteine ligase (GCL) gene is provided. The fly displays phenotypes associated with Alzheimer's disease (AD). Further, a method for diagnosing AD is provided, which includes assessing enzymatic activities in mitochondrial enzymes. Glutathione pathway are investigated by creating Alzheimer's model Drosophila with over-expression of the GCLc gene, inducing redox stress through sleep deprivation, and analyzing mitochondrial electron transport chain (ETC) using colorimetric enzymatic assays. For prevention of AD, it is proposed that the epigenetic approaches be used to increase glutathione levels in vivo before the onset of AD. For treatment of AD, it is proposed that the glutathione levels be increased by GCLc modulation.

Abstract: The present invention provides transgenic non-human animals and non-human mammalian somatic and germ cells harbouring a human DNA sequence encoding Alzheimer's Disease (AD) derived tau protein, capable of inducing AD pathology in transgenic animals. Alzheimer's tau protein is expressed on specific genetic backgrounds allowing also simulation of different human diseases including hypertension, diabetes, hyper-cholesterolemia, which are associated with neurodegeneration and are considerable risk factors for AD development. Transgenic animals and cells of the invention exhibit neurofibrillary pathology and may serve as in vivo and in vitro assay systems for screening and developing therapeutic and preventive substances and also diagnostic markers and probes for tauopathies and AD.

Abstract: The present invention describes a novel transgenic mouse model for the common sporadic form of Alzheimer's disease. More particularly, the invention relates to a nucleotide sequence encoding A? 4-42 in functional linkage with at least a promoter, signal peptide sequence and a polyadenylation signal sequence, a cell and a transgenic non-human animal comprising said nucleotide sequence, and their respective use in screening methods.

Abstract: Provided are non-human mammals comprising a knock-in nucleic acid sequence capable of causing an alteration of expression of wild-type Bri2 in the mammal or a knockout of wild-type Bri2. Also provided are the non-human mammals as a model for Alzheimer's disease.

Abstract: The present invention relates to methods of treatment of clinical disorders associated with protein aggregation comprising administering, to a subject, an effective amount of an anti-protein aggregate (“APA”) compound selected from the group consisting of pimozide, fluphenazine (e.g., fluphenazine hydrochloride), tamoxifen (e.g., tamoxifen citrate), taxol, cantharidin, cantharidic acid, salts thereof and their structurally related compounds. It is based, at least in part, on the discovery that each of the aforelisted compounds were able to promote degradation of aggregated ATZ protein in a Caenorhabditis elegans model system. According to the invention, treatment with one or more of these APA compounds may be used to ameliorate the symptoms and signs of AT deficiency as well as other disorders marked by protein aggregation, including, but not limited to, Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.

Abstract: Methods and kits for identifying neurological conditions in a patient by determining a level of expression of dynactin subunit p62 are disclosed. The neurological conditions may include, for example, Alzheimer's Disease (AD) without cerebral amyloid angiopathy (CAA).

Abstract: The present invention provides compositions of insulin-like growth factor II (IGF-II) peptides or nucleic acids for the treatment of memory disorders and to enhance memory in subjects in need thereof.

Abstract: The present invention provides transgenic non-human animals and non-human mammalian somatic and germ cells harbouring a human DNA sequence encoding Alzheimer's Disease (AD) derived tau protein, capable of inducing AD pathology in transgenic animals. Alzheimer's tau protein is expressed on specific genetic backgrounds allowing also simulation of different human diseases including hypertension, diabetes, hyper-cholesterolemia, which are associated with neurodegeneration and are considerable risk factors for AD development. Transgenic animals and cells of the present invention exhibit neurofibrillary pathology and may serve as in vivo and also in vitro assay systems for screening and developing therapeutic and preventive substances and also diagnostic markers and probes for tauopathies and AD.

Abstract: Transgenic mammals, cells derived from the animals, and methods of using these to monitor the endoplasmic reticulum (ER) stress response are provided. In some embodiments, the methods allow for monitoring the ER stress response in real time. Some of the methods allow non-invasive in vivo visualization of ER stress response. Also provided are methods of screening molecules and/or treatment conditions for the ability to modulate the ER stress response, methods of treating diseases characterized by ER stress response activity, and methods of detecting the toxicity or therapeutic ratio of molecules that modulate the ER stress response.

Abstract: The present invention relates to a method for identifying an inhibitor of the aggregation of amyloid-? peptide (A?), comprising the steps of a) contacting at least one A?-peptide and/or the nitrated forms thereof with at least one candidate inhibitor that potentially specifically binds to a region in said A?-peptide capable of being nitrated, and b) detecting said inhibitor specifically binding to said region in said A?-peptide through detecting a lack of or a reduced aggregation of said at least one A?-peptide. The present invention is further directed at improved methods for treating neuronal degradation and particularly Alzheimer's disease, based on said inhibitor. The present invention is further directed at methods for diagnosing the aggregation of A?-peptide in the context of neuronal degradation and particularly Alzheimer's disease.

Abstract: The present invention provides a transgenic animal model of Alzheimer's Disease designated TgCRND8 as well as a method for making such model, which allows for the characterization of the etiology of the disease as well as for provide a system for the development and testing of potential treatments.

Abstract: The present invention discloses a non-human animal model for a hereditary autosomal dominant disease. The non-human animal model expresses at least one phenotype associated with the disease and is obtained by a genetic determinant. The invention also relates to sperm cells and embryos comprising the genetic determinant for an autosomal dominant disease. Furthermore, methods for producing the non-human animal model, sperm cell, and embryos are disclosed.

Abstract: Provided is a novel APP (amyloid precursor protein) transgenic non-human animal modeling in vivo the pathophysiological effects and effects on cognitive behavior of early intraneuronal and extracellular brain parenchymal amyloid-? (A?) deposition and cerebral amyloid angiopathy associated with brain microhemorrhages and reduced vasoreactivity and blood flow. Furthermore, methods of screening for therapeutic or diagnostic agents useful in the treatment or diagnosis of Alzheimer's disease, in particular for improving blood flow to the brain are provided as well as the corresponding therapeutic methods.

Abstract: The present invention relates to methods and compositions for high content drug screening in C. elegans which may be used to identify compounds that treat disorders associated with protein aggregation.

Abstract: The present invention provides a transgenic animal model of Alzheimer's Disease designated TgCRND8 as well as a method for making such model, which allows for the characterization of the etiology of the disease as well as for provide a system for the development and testing of potential treatments.

Abstract: The invention provides monomeric and oligomeric amyloid beta peptide isomers that are resistant towards fibrillogenesis and their use as screening reagents or antigens in methods and pharmaceutical preparations for the treatment of Alzheimer's disease and other conditions related to protein misfolding. The alanines at positions 21 and 30, in wild type amyloid beta peptide amino acid sequence, are according to the invention replaced by cysteins, which results in an intra molecular disulphide bond. The invention further provides transgenic animals expressing modified amyloid precursor proteins or amyloid beta peptides.

Abstract: Provided are non-human mammals comprising a transgenic nucleic acid sequence capable of causing an alteration of expression of Bri2 or Bri3 in the mammal. Also provided are non-human mammals comprising a Bri2 or Bri3 gene under the control of the native Bri2 or Bri3 promoter. Additionally provided are non-human mammals genetically engineered to lack expression of a Bri2 or Bri3 gene. Further, non-human mammals comprising a transgene encoding a Bri2 or Bri3 protein under the control of the ?CaMKII promoter are provided. Non-human mammals comprising a transgene encoding a furin protein are additionally provided. Embryonic stem cells of any of the above-described non-human mammals are further provided. Methods of screening a compound for treatment of a disease characterized by cerebral amyloidosis are additionally provided. Also provided are methods of making transgenic non-human mammals.

Abstract: The invention provides non-human transgenic animals as models of neurodegenerative brain pathology, including, but not limited to, Alzheimer's disease (AD), and cancer. The non-human transgenic animals of the present invention include an exogenous DNA that reduces or eliminates the expression and/or function of a molecular chaperone, including, but not limited to heat shock protein 110 (Hsp1 10) or heat shock protein 70 (Hsp70). These non-human transgenic animals may be used in methods of screening and identifying compounds useful for the prevention and/or treatment of neurodegenerative brain pathology and/or cancer.

Abstract: The present invention relates to a transgenic animal suitable for modelling Alzheimer's Disease. The present invention also relates to cells and gametes of the transgenic animal of the invention, along with nucleic acids and vectors suitable for generating the transgenic animal. Methods of generating the transgenic animal are also described, along with screening methods utilizing the transgenic animal.

Abstract: The present invention discloses a dysregulation of the KCNN3 gene and the protein products thereof in Alzheimer's disease patients and individuals being at risk of developing Alzheimer's disease. Based on this finding, the invention provides methods for diagnosing and prognosticating Alzheimer's disease in a subject, and for determining whether a subject is at increased risk of developing Alzheimer's disease. Furthermore, this invention provides therapeutic and prophylactic methods for treating and preventing Alzheimer's disease and related neurodegenerative disorders using the KCNN3 gene and its corresponding gene products. Screening methods for modulating agents of neurodegenerative diseases are also disclosed.

Abstract: The present invention discloses a double transgenic fly that expresses both Tau protein and the human A?42 peptide of human amyloid-? precursor protein (APP). The double transgenic flies of the present invention display a synergistic altered phenotype as compared to the altered phenotype displayed by transgenic flies expressing either Tau or human A?42 alone, and thus provide for an improved model for neurodegenerative disorders, such as Alzheimer's disease. The invention further discloses methods for identifying for therapeutic compounds to treat neurodegenerative disorders using the double transgenic flies.

Abstract: Disclosed is a method of inducing or modeling a disease associated with pathological tau protein aggregation. The method can be carried out in vitro and animal models, and may be used to screen for therapeutic, prognostic or diagnostic agents.

Abstract: The present invention relates to Glycine N-methyltransferase (GNMT) animal model and use thereof.

Abstract: The invention relates to methylated proteins that control protein phosphorylation, particularly phosphoesterases, such as PP2A. It relates to screening methods for determining agents that affect methylation of these proteins and thus also modulate the level of phosphorylation of phosphoproteins. It relates as well to the agents and to compositions comprising the agents. In a particular aspect in this regard the invention relates to agents that alter PP2A methylation and that thereby affect phosphorylation of phosphoproteins that play an important role in health or disease, such as the tau protein which is implicated in the etiology of Alzheimer's Disease. The invention further relates to diagnostic methods based on protein methylation levels, to compositions comprising agents for affecting methylation of proteins and for controlling the phosphate complement of phosphoproteins.

Abstract: The present invention provides a transgenic animal model of Alzheimer's Disease designated TgCRND8 as well as a method for making such model, which allows for the characterization of the etiology of the disease as well as for provide a system for the development and testing of potential treatments.

Abstract: The present invention provides a non-human model mammal of Alzheimer's disease (AD) containing chimeric amyloid precursor protein (APP) gene capable of producing human amyloid ? peptide (A?) or a living part thereof, characterized in that A?42/A?40 ratio at 8-weeks-old is about 7-fold or more (about 140-fold or more in homozygote) higher compared to that of a corresponding wild-type mammal. Moreover, the present invention provides the mammal or a living part thereof, further characterized in that the level of APP expression is not significantly different compared to the corresponding wild-type mammal, and a screening method for a prophylactic and/or therapeutic drug for AD, a biomarker in biological fluids and molecular imaging of amyloid deposition or other pathological changes in the brain for an early diagnosis of AD using the mammal or a living part thereof.

Abstract: The present invention relates to a modified pig as a model for studying Alzheimer's disease. The modified pig model displays one or more phenotypes associated with Alzheimer's disease. Disclosed is also a modified pig comprising a modified human and/or porcine APP gene, and/or PS1 gene, and/or a transcriptional and/or translational product or part thereof. The invention further relates to methods for producing the modified pig; and methods for evaluating the effect of a therapeutical treatment of Alzheimer's disease; methods for screening the efficacy of a pharmaceutical composition; and a method for treatment of a human being suffering from Alzheimer's disease are disclosed.

Abstract: A transgenic non-human animal expressing at least one transgene including a DNA sequence encoding a heterologous Amyloid Precursor Protein (APP) including at least the Arctic mutation (E693G) and a further AD (Alzheimer's disease) pathogenic mutation or a further transgene affecting AD pathogenesis, which results in increased amounts of intracellular soluble A aggregates, including A peptides. The method of producing the transgenic animal, and methods of screening for therapeutic or diagnostic agents useful in treatment or diagnosis of Alzheimer's disease are also disclosed.

Abstract: Animal model involving transgenic manipulation of amyloid precursor protein, useful for testing potential therapeutic agents for the treatment of neurodegenerative disorders, in particular Alzheimer's disease.

Abstract: The invention provides transgenic non-human animals and transgenic non-human mammalian cells harboring a transgene encoding an APP polypeptide comprising the Swedish mutation.