Cysteine Content

The three major isoforms differ in cysteine content: apoE4, apoE3, and apoE2 contain 0, 1, and 2 cysteines, respectively. As a result, apoE2 and apoE3 can form both disulfide-linked homodimers and heterodimers with apoA-II. In apoE3/3 subjects, approximately 50% of the apoE3 exists in one of these disulfide-linked forms. In addition, the apoE3 homodimer is present in cerebrospinal fluid. These disulfide-linked dimers affect lipid-binding properties and interaction with LDL receptors, but their effect in neurobiology has not been systematically assessed. Since mouse apoE also lacks cysteine, a future objective will be to use gene targeting to introduce a cysteine codon to produce the functional equivalent of apoE3 and determine its effect on neurodegeneration.

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