An in vitro method of identifying an agent that reduces apolipoprotein E (apoE) neurotoxic polypeptide-induced impairment of mitochondrial integrity and/or function, the method comprising: a) contacting a neuronal cell in vitro with a test agent; and b) determining the effect, if any, of the test agent on mitochondrial integrity and/or function, wherein a reduction in apoE-induced impairment of mitochondrial integrity and/or function, compared to mitochondrial integrity and/or function in the absence of the test agent, indicates that the test agent reduces apoE-induced impairment of mitochondrial integrity and/or function; wherein either: A): the neuronal cell has been genetically modified with an expression vector that comprises a nucleotide sequence encoding a neurotoxic apoE polypeptide, wherein the toxic apoE polypeptide: i) consists of amino acids 1-272 of the amino acid sequence set forth in SEQ ID NO:1; or ii) comprises the amino acid sequence set forth in SEQ ID NO: 1 having an amino acid substitution selected from: L279Q, K282A and Q284A; wherein said nucleotide sequence is operably linked to a promoter functional in a eukaryotic host cell, wherein the neurotoxic apoE polypeptide is present in the cytosol of the cell; and said determining is performed by contacting the cell with a fluorescent dye that is an indicator of mitochondrial function and/or integrity; or B): the neuronal cell is as defined in A, above, and is also genetically modified with a nucleic acid comprising a nucleotide sequence encoding a mitochondrial indicator polypeptide comprising an amino acid sequence that provides for mitochondrial localization; and said determining is performed by detecting the mitochondrial indicator polypeptide. a) contacting a neuronal cell in vitro with a test agent; and b) determining the effect, if any, of the test agent on mitochondrial integrity and/or function, wherein a reduction in apoE-induced impairment of mitochondrial integrity and/or function, compared to mitochondrial integrity and/or function in the absence of the test agent, indicates that the test agent reduces apoE-induced impairment of mitochondrial integrity and/or function; A): the neuronal cell has been genetically modified with an expression vector that comprises a nucleotide sequence encoding a neurotoxic apoE polypeptide, wherein the toxic apoE polypeptide: i) consists of amino acids 1-272 of the amino acid sequence set forth in SEQ ID NO:1; or ii) comprises the amino acid sequence set forth in SEQ ID NO: 1 having an amino acid substitution selected from: L279Q, K282A and Q284A; wherein said nucleotide sequence is operably linked to a promoter functional in a eukaryotic host cell, wherein the neurotoxic apoE polypeptide is present in the cytosol of the cell; and said determining is performed by contacting the cell with a fluorescent dye that is an indicator of mitochondrial function and/or integrity; or i) consists of amino acids 1-272 of the amino acid sequence set forth in SEQ ID NO:1; or ii) comprises the amino acid sequence set forth in SEQ ID NO: 1 having an amino acid substitution selected from: L279Q, K282A and Q284A; B): the neuronal cell is as defined in A, above, and is also genetically modified with a nucleic acid comprising a nucleotide sequence encoding a mitochondrial indicator polypeptide comprising an amino acid sequence that provides for mitochondrial localization; and said determining is performed by detecting the mitochondrial indicator polypeptide.