Methods of treating disorders related to apoE

A method of inhibiting formation of neurofibrillary tangles in a neuronal cell of an individual, the method comprising:

• contacting the neuronal cell with a peptide that inhibits an enzymatic activity of an enzyme in the neuronal cell that catalyzes cleavage of apoE in the cell to generate neurotoxic carboxyl-terminal truncated apoE, wherein the carboxyl-terminal truncated apoE comprises amino acids 244-260 of apoE, and wherein the peptide is 4 to 6 amino acid residues in length.

A method of reducing the level of carboxyl-terminal truncated apoE in a neuronal cell, the method comprising:

• contacting the cell with a peptide that reduces activation of an enzyme that catalyzes the formation of neurotoxic carboxyl-terminal truncated apoE in a neuronal cell, wherein said enzyme is activated by Aβ1-42, wherein the carboxyl-terminal truncated apoE comprises amino acids 244-260 of apoE, wherein the peptide is 4 to 6 amino acid residues in length, and wherein a reduction in the activation of the enzyme results in a reduction in the level of neurotoxic carboxyl-terminal truncated apoE in the cell.

A method of reducing formation of neurotoxic carboxyl-terminal apoE in a neuronal cell in an individual, the method comprising contacting the cell with a peptide that reduces formation of carboxyl-terminal truncated apoE in the individual, wherein the carboxyl-terminal truncated apoE comprises amino acids 244-260 of apoE, wherein the peptide is 4 or 5 amino acid residues in length, and wherein formation of neurotoxic carboxyl-terminal truncated apoE in the cell is reduced.

A method of treating Alzheimer's disease (AD), the method comprising administering a peptide selected from the group consisting of Ala-Ala-Pro-Phe (SEQ ID NO:

• 1), Ala-Ala-Pro-Leu (SEQ ID NO:
• 3), and Ala-Ala-Ala-Ala-Pro-Phe (SEQ ID NO:
• 4) in an amount effective to inhibit an enzyme that catalyzes the formation of carboxyl-terminal truncated apoE in a neuronal cell of an individual having AD, wherein the carboxyl-terminal truncated apoE comprises amino acids 244-260 of apoE, and wherein the enzyme is inhibited, and the level of carboxyl-terminal truncated apoE in a neuronal cell in the individual is reduced.