Retinoic acid induced differentiated neuroblastoma cells show increased expression of the βA4 amyloid gene of Alzheimer's disease and an altered splicing pattern

Abstract

Retinoic add (RA) induced differentiation of SH‐SY5Y neuroblastoma cells is associated with more than a tenfold induction of total Alzheimer's disease βA4 amyloid protein precursor (APP) mRNA as analyzed by Northern blot hybridisation. Sl nuelease protection experiments reveal that the splicing pattern of these differentiated cells is altered in favor of APP₆₉₅ mRNA, coding for the shortest amyloidogenic βA4 amyloid precursor protein. Induction of differentiation of SH‐SY5Y cells with NGF leads to a fivefold increase of total APP mRNA without change in the splicing pattern. This suggests that RA but not NGF induces factor(s) which are responsible for an APP hnRNA splicing favoring APP₆₉₅ mRNA.