Apolipoprotein E and Tau phosphorylation in human neuroblastoma cells.

Phosphorylation is the major post-translational modification of Tau proteins and it plays an important role in Tau biological functions. Hyperphosphorylation of these proteins occurs during neurodegenerative disorders such as Alzheimer's disease. It was hypothesized that some variants of apolipoprotein E (apo E) may have a protective effect against the normal or pathological phosphorylation of Tau proteins. We have recently shown that apo E synthesis occurs in human SY 5Y and Kelly neuroblastoma cell lines which express different isoforms (E3 for SY 5Y; E3 and E4 for Kelly) [Dupont-Wallois, L., Soulié, C., Sergeant, N., Wavrant-de Wrieze, F., Chartier-Harlin, M.C., Delacourte, A. and Caillet-Boudin, M.L., Neurobiol. Dis., 4 (1997) 356-364]. Therefore, this cellular model makes it possible to study the differential influence, if any, of apo E3 and E4 on Tau phosphorylation. Using a large panel of Tau phosphorylation-dependent antibodies, we were not able to detect a significant difference in Tau immunoreactivity linked to the different apo E genotypes, even when the hyperphosphorylation of Tau proteins was induced by treating cells with Okadaic acid (OA), an inhibitor of phosphatase 1 and 2A proteins. Thus, a difference in apo E isoforms had no dramatic effect upon Tau phosphorylation in native or OA treated cells.