Mice transgenic for human APOE2, E3, and E4 alleles express native 34- kDa human apoE and two sialylated apoE isoproteins with approximate molecular weights of 37 kDa (apoE(s)) and 39 kDa (apoE(s2)) in brain. These multiple apoE/apoE(s)/apoE(s2) band patterns on Western blot are also observed in human brain, but are not seen in wild-type mouse brain. Both the 37-kDa apoE(s) and 39-kDa apoE(s2) are coprecipitated with native 34-kDa apoE by antibody to human apoE. Neuraminidase digestion eliminates the 37- and 39- kDa forms and results in a downward shift in the bands to the position of the 34-kDa native form. These sialylated apoE isoproteins are found preferentially associated with neurons and contribute significantly (50-60%) to the total neuronal apoE in neuronal cultures from transgenic mice, while only 5-10% of total apoE is sialylated in cultures enriched in glial cells. In situ hybridization and immunocytochemistry demonstrate apoE mRNA and apoE immunoreactivity are predominantly located in cell soma of neurons, not in neuronal processes.
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