Abstract: The present invention aims to provide a pharmaceutical agent for the prophylaxis and/or treatment of Alzheimer's disease, which has a novel action mechanism and shows less side effects. A polyphenol derivative having liposolubility enhanced by the introduction of at least one kind of a liposoluble group selected from the group consisting of a chain saturated hydrocarbon group, a chain unsaturated hydrocarbon group, a cyclic saturated hydrocarbon group, a cyclic unsaturated hydrocarbon group, an aromatic hydrocarbon group, a liposoluble vitamin residue and a sterol residue has an action to potentiate neprilysin activity, and is useful as a pharmaceutical agent for the prophylaxis and/or treatment of Alzheimer's disease.

Abstract: The present invention aims to provide a pharmaceutical agent for the prophylaxis and/or treatment of Alzheimer's disease, which has a novel action mechanism and shows less side effects. A polyphenol derivative having liposolubility enhanced by the introduction of at least one kind of a liposoluble group selected from the group consisting of a chain saturated hydrocarbon group, a chain unsaturated hydrocarbon group, a cyclic saturated hydrocarbon group, a cyclic unsaturated hydrocarbon group, an aromatic hydrocarbon group, a liposoluble vitamin residue and a sterol residue has an action to potentiate neprilysin activity, and is useful as a pharmaceutical agent for the prophylaxis and/or treatment of Alzheimer's disease.

Abstract: The present invention provides a method for screening a therapeutic and/or prophylactic agent for Alzheimer's disease using at least one index selected from the levels of A? oligomers, BiP, cleaved caspase 4, PRDX4 and ROS in nerve cells or the like whose differentiation has been induced from iPS cells derived from somatic cells of a patient with Alzheimer's disease.

Abstract: The present invention provides a method for detecting onset of, or the risk of development of, a protein misfolding disease, and a method for predicting the age of onset of a protein misfolding disease using nerve cells derived from iPS cells. The present invention also provides a kit to be used in these methods.

Abstract: The present invention provides a method for screening a therapeutic and/or prophylactic agent for Alzheimer's disease using at least one index selected from the group consisting of the levels of A? oligomers, BiP, cleaved caspase 4, PRDX4 and ROS in nerve cells or the like whose differentiation has been induced from iPS cells derived from somatic cells of a patient with Alzheimer's disease.

Abstract: The present invention provides a method for detecting onset of, or the risk of development of, a protein misfolding disease, and a method for predicting the age of onset of a protein misfolding disease using nerve cells derived from iPS cells. The present invention also provides a kit to be used in these methods.

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 provides a method of measuring the activity of neprilysin, etc. More specifically, the present invention provides a method of measuring the activity of neprilysin in nerve cells; a method of screening a protein, a peptide or a compound enhancing the activity or expression of neprilysin in nerve cells by measuring the activity of neprilysin; a method of enhancing the activity or expression of neprilysin; and so on. Thus, the compound enhancing the activity and/or expression of neprilysin, which is obtained by the screening method characterized by using the method of measuring the activity of neprilysin in accordance with the present invention, is useful as a preventive and/or therapeutic agent for Alzheimer's disease. The method of measuring the activity of the present invention can be used for presymptomatic diagnosis of Alzheimer's disease.

Abstract: The present invention provides a method of measuring the activity of neprilysin, etc. More specifically, the present invention provides a method of measuring the activity of neprilysin in nerve cells; a method of screening a protein, a peptide or a compound enhancing the activity or expression of neprilysin nerve cells by measuring the activity of neprilysin; a method of enhancing the activity or expression of neprilysin; and so on. Thus, the compound enhancing the activity and/or expression of neprilysin, which is obtained by the screening method characterized by using the method of measuring the activity of neprilysin in accordance with the present invention, is useful as a preventive and/or therapeutic agent for Alzheimer's disease. The method of measuring the activity of the present invention can be used for presymptoms diagnosis of Alzheimer's disease.

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 provides a method of measuring the activity of neprilysin, etc. More specifically, the present invention provides a method of measuring the activity of neprilysin in nerve cells; a method of screening a protein, a peptide or a compound enhancing the activity or expression of neprilysin nerve cells by measuring the activity of neprilysin; a method of enhancing the activity or expression of neprilysin; and so on. Thus, the compound enhancing the activity and/or expression of neprilysin, which is obtained by the screening method characterized by using the method of measuring the activity of neprilysin in accordance with the present invention, is useful as a preventive and/or therapeutic agent for Alzheimer's disease. The method of measuring the activity of the present invention can be used for presymptoms diagnosis of Alzheimer's disease.