Abstract: The present disclosure provides a method of increasing the functionality of a GABAergic interneuron in the hilus of the hippocampus of an individual having at least one apolipoprotein E4 (apoE4) allele. The method generally involves reducing tau levels in the interneuron.

Abstract: The present disclosure provides methods of identifying a candidate agent for treating an apoE-associated neurodegenerative disorder. The methods involve contacting a PCSK1 or a PCSK2 polypeptide with an apolipoprotein E polypeptide in the presence of a test agent.

Abstract: The present disclosure provides methods of generating neural stem cells from differentiated somatic cells. The present disclosure also provides induced neural stem cells generated using a subject method, as well as differentiated cells generated from a subject induced neural stem cell. A subject neural stem cell, as well as differentiated cells derived from a subject neural stem cell, is useful in various applications, which are also provided in the present disclosure.

Abstract: The present disclosure provides a method of increasing the functionality of a GABAergic interneuron in the hilus of the hippocampus of an individual having at least one apolipoprotein E4 (apoE4) allele. The method generally involves reducing tau levels in the interneuron.

Abstract: The present disclosure provides synthetic antibodies specific for an epitope present on an apolipoprotein E polypeptide. The antibodies are useful in various treatment, diagnostic, and monitoring applications, which are also provided.

Abstract: The present disclosure provides methods of generating neural stem cells from differentiated somatic cells. The present disclosure also provides induced neural stem cells generated using a subject method, as well as differentiated cells generated from a subject induced neural stem cell. A subject neural stem cell, as well as differentiated cells derived from a subject neural stem cell, is useful in various applications, which are also provided in the present disclosure.

Abstract: The present disclosure provides methods of generating neural stem cells from differentiated somatic cells. The present disclosure also provides induced neural stem cells generated using a subject method, as well as differentiated cells generated from a subject induced neural stem cell. A subject neural stem cell, as well as differentiated cells derived from a subject neural stem cell, is useful in various applications, which are also provided in the present disclosure.

Abstract: The present invention provides isolated cells comprising a nucleic acid encoding a toxic form of apoE. The present invention further provides screening methods for identifying compounds that reduce apoE-induced impairment of mitochondrial integrity and/or function. The present invention further provides kits for use in carrying out a subject screening method. The present invention provides agents that reduce apoE-induced impairment of mitochondrial integrity and/or function; and use of such agents in the treatment of apoE-related disorders.

Abstract: The present disclosure provides synthetic antibodies specific for an epitope present on an apolipoprotein E polypeptide. The antibodies are useful in various treatment, diagnostic, and monitoring applications, which are also provided.

Abstract: The present disclosure provides methods of generating neural stem cells from differentiated somatic cells. The present disclosure also provides induced neural stem cells generated using a subject method, as well as differentiated cells generated from a subject induced neural stem cell. A subject neural stem cell, as well as differentiated cells derived from a subject neural stem cell, is useful in various applications, which are also provided in the present disclosure.

Abstract: The present invention provides methods for treating apoE-related disorders. The methods generally involve administering an effective amount of an agent that inhibits activity of an enzyme that cleaves apoE.

Abstract: The present invention provides compounds that inhibit apoE4 domain interaction; and compositions, including pharmaceutical compositions, comprising the compounds. The present invention provides methods of treating apoE4-related disorders. The methods generally involve administering to an individual in need thereof a therapeutically effective amount of an apoE4 domain interaction inhibitor.

Abstract: The present disclosure provides methods of reducing apoE4 fragment-mediated toxicity of interneurons, e.g, GABAergic interneurons. The present disclosure provides methods of treating apoE4-mediated neurological disorders in an apoE4-positive individual.

Abstract: The present disclosure provides a method of increasing the functionality of a GABAergic interneuron in the hilus of the hippocampus of an individual having at least one apolipoprotein E4 (apoE4) allele. The method generally involves reducing tau levels in the interneuron.

Abstract: The present invention provides nucleic acids comprising a nucleotide sequence encoding an apolipoprotein E (apoE) splice variant, e.g., an unprocessed apoE, that retains intron 3; and vectors and host cells comprising same. The present invention further provides screening methods to identify agents that inhibit cleavage of intron-3 from the apoE splice variant. The present invention further provides methods of treating apoE-related neurological disorders, involving administering an agent that inhibits removal of intron-3 from a precursor apoE mRNA.

Abstract: The present invention provides methods inhibiting formation of neurofibrillary tangles; and methods for treating disorders relating to apolipoprotein E (apoE) in a subject. The methods generally involve reducing the level of a carboxyl-terminal truncated form of apoE in a neuronal cell of a subject. The invention further provides isolated cells comprising a nucleic acid molecule encoding a carboxyl-terminal truncated form of apoE; and methods of screening compounds using the cells. The invention further provides compounds that inhibit an apoE cleavage enzyme, and that reduce the formation of neurofibrillary tangles in a neuronal cell. The invention further provides transgenic non-human animals that include as a transgene a nucleic acid that encodes a carboxyl-terminal truncated form of apoE; as well as methods of screening compounds using transgenic animals.

Abstract: The present invention provides methods of diagnosing Alzheimer's Disease in a subject. The methods generally involve detecting carboxyl-terminal truncated forms of apoE in a biological sample from the subject. The present invention further provides kits for carrying out the diagnostic methods of the invention.

Abstract: The present invention provides a selected population of neural cells, including neural stem cells, neural progenitor cells, neural precursor cells, and progeny thereof, which neural cells are selected for an apoE4? phenotype. In some embodiments, the neural cells are further selected for an apoE3+ phenotype. The selected population of neural cells is useful in treating various disorders, such as neurodegenerative disorders and demyelination diseases. The present invention further provides methods of treating neurodegenerative disorders and demyelinating diseases, generally involving administering a subject selected cell population.

Abstract: The present invention provides isolated cells comprising a nucleic acid encoding a toxic form of apoE. The present invention further provides screening methods for identifying compounds that reduce apoE-induced impairment of mitochondrial integrity and/or function. The present invention further provides kits for use in carrying out a subject screening method. The present invention provides agents that reduce apoE-induced impairment of mitochondrial integrity and/or function; and use of such agents in the treatment of apoE-related disorders.

Abstract: The present invention provides nucleic acids comprising a nucleotide sequence encoding an apolipoprotein E (apoE) splice variant, e.g., an unprocessed apoE, that retains intron 3; and vectors and host cells comprising same. The present invention further provides screening methods to identify agents that inhibit cleavage of intron-3 from the apoE splice variant. The present invention further provides methods of treating apoE-related neurological disorders, involving administering an agent that inhibits removal of intron-3 from a precursor apoE mRNA.