JPWO2020260471A5 - - Google Patents

Claims (19)

A fragment of apolipoprotein E consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:3. 2. A fragment according to claim 1, consisting of the amino acid sequence of SEQ ID NO:2. 2. A fragment according to claim 1, consisting of the amino acid sequence of SEQ ID NO:3. A fragment according to any one of claims 1 to 3, which exhibits neurotoxicity. An isolated nucleic acid encoding a fragment according to any one of claims 1-4. A vector comprising the isolated nucleic acid of claim 5. A host cell containing the vector of claim 6 . A transgenic non-human animal comprising the vector of claim 6. A vaccine comprising an apolipoprotein E fragment consisting of the amino acid sequence of any one of SEQ ID NOS: 1-3. 10. A composition for preventing or treating neurological diseases, said composition comprising the vaccine of claim 9. A method for screening a pharmacological agent capable of modulating neuronal toxicity of an apolipoprotein E fragment consisting of an amino acid sequence of any one of SEQ ID NOs: 1 to 3, comprising:
A method comprising contacting a neuronal cell or non-human animal with a candidate pharmacological agent in the presence of said fragment and detecting neuronal toxicity or neuronal cell death. A method of screening for a pharmacological agent capable of regulating the production of an apolipoprotein E fragment consisting of an amino acid sequence of any one of SEQ ID NOS: 1-3, comprising:
A method comprising contacting a neuronal cell expressing apolipoprotein E with a candidate pharmacological agent and detecting the amount of said fragment. 13. The method of claim 12, wherein said neural cell expresses said apolipoprotein E fragment. 13. The method of claim 12, wherein said neural cell expresses full-length apolipoprotein E. 15. The method of claim 14, wherein said apolipoprotein E is apolipoprotein E4 (ApoE4). The screening method according to any one of claims 12 to 15, wherein the neural cells expressing the apolipoprotein E fragment or full-length protein are genetically modified cells. A method for detecting the presence or amount of an apolipoprotein E fragment consisting of an amino acid sequence of any one of SEQ ID NOs: 1 to 3 in a subject, comprising:
A method comprising contacting a sample obtained from said subject with an aptamer that binds said fragment, and detecting the presence or amount of said fragment in said sample. 18. The method of claim 17, wherein the sample is obtained from a subject having or suspected of having Alzheimer's disease (AD) or mild cognitive impairment (MCI). 19. The method of claim 17 or 18, wherein said presence or amount of said apolipoprotein E fragment is used to detect, diagnose, or assist in diagnosing AD or MCI.