Isoform-specific interactions of apolipoprotein E with the microtubule-associated protein MAP2c: implications for Alzheimer's disease

The apolipoprotein E type 4 allele is a susceptibility gene for late-onset Alzheimer's disease. Apolipoprotein E is found in neurons, some of which contain paired helical filaments made of the microtubule-associated protein τ. Previous studies have demonstrated that the apoE3 isoform, but not the apoE4 isoform, binds τ with high avidity. Because the microtubule-associated protein MAP2c also effects microtubule assembly and stability, we examined interactions between apoE isoforms and MAP2c. Similar to the τ-binding results, apoE3, but not apoE4, bound MAP2c. Binding was detectable down to 10^-9 M MAP2c and 10^-8 M apoE3. Isoform-specific interactions of apoE with the microtubule-associated proteins MAP2c and τ might affect intracellular maintenance of microtubules and could contribute to a time-dependent pathogenesis of Alzheimer's disease.