The present invention provides methods, kits, and compositions for purifying HDL molecules from a sample (e.g., blood sample) using HDL tagging molecules comprising an HDL lipophilic core binding peptide (e.g., portion of ApoA1) and an affinity tag. The present invention also provides methods, kits, and compositions for detecting non-fragmented ApoA1 with mass spectrometry. The present invention further provides methods, kits, and compositions for tagging HDL molecules in a sample with detectably labeled ApoA1 molecules such that the ratio of detectably labeled ApoA1 molecules to native ApoA1 proteins may be determined.

The present invention provides methods, kits, and compositions for purifying HDL molecules from a sample (e.g., blood sample) using HDL tagging molecules comprising an HDL lipophilic core binding peptide (e.g., portion of ApoA1) and an affinity tag. The present invention also provides methods, kits, and compositions for detecting non-fragmented ApoA1 with mass spectrometry. The present invention further provides methods, kits, and compositions for tagging HDL molecules in a sample with detectably labeled ApoA1 molecules such that the ratio of detectably labeled ApoA1 molecules to native ApoA1 proteins may be determined.

The instant disclosure provides antibodies that specifically bind to ApoC3 (e.g., human ApoC3) and antagonize ApoC3 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

The present disclosure provides methods of treating Alzheimer's Disease (AD) and rescuing cognitive deficits associated with AD in a subject having an apoE4/4 genotype, by administering a therapeutically effective amount of the loop-diuretic bumetanide to the subject. Also disclosed are kits for performing the method, including one or more doses of a bumetanide formulation; and which may also include instructions for treating a patient having an apoE4/4 genotype by administering bumetanide, and/or instructions and reagents for testing/identifying a subject having an apoE4/4 genotype.

A peptide for treating rheumatoid arthritis and use thereof are provided, and a peptide consisting of an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3, or SEQ ID NO: 5 or a polynucleotide encoding the same, and a pharmaceutical composition for treating rheumatoid arthritis or a health functional food composition for improving rheumatoid arthritis, each including the peptide, are provided.

Described herein are fusion peptides comprising (i) a peptide sequence comprising the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:24 or a fragment or derivative thereof, or a sequence at least about 80% identical thereto and (ii) an endosomal escape domain. Such fusion peptides can be conjugated with an active agent to deliver the active agent across the blood-brain barrier to the central nervous system and across blood-ocular barriers to the eye.

Described herein are fusion peptides comprising (i) a peptide sequence comprising the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:24 or a fragment or derivative thereof, or a sequence at least about 80% identical thereto and (ii) an endosomal escape domain. Such fusion peptides can be conjugated with an active agent to deliver the active agent across the blood-brain barrier to the central nervous system and across blood-ocular barriers to the eye.

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimer's Disease or frontotemporal dementia.

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimer's Disease or frontotemporal dementia.

The present disclosure provides a genetically modified mouse comprising a genomic nucleic acid encoding human APOE4, a genomic nucleic acid encoding mouse TREM2 modified to include a R47H substitution, and at least one genomic modification selected from the group consisting of: (a) a genomic nucleic acid encoding mouse ABCA7 modified to include an A 1541 G substitution; (b) a genomic nucleic acid encoding mouse APP modified to include G601R, F606Y, and R609H substitutions; (c) a genomic nucleic acid encoding mouse PLCG2 modified to include a M28L substitution; (d) a genomic nucleic acid encoding mouse MTHFR modified to include a A262V substitution; (e) an inactivated Ceacam1 allele; and (f) an inactivated Il1rap allele. Methods of producing the genetically modified mouse and methods of using the genetically modified mouse are also provided.