OLIGODENDROCYTES EXPRESS DIFFERENT ISOFORMS OF BETA-AMYLOID PRECURSORPROTEIN IN CHEMICALLY-DEFINED CELL-CULTURE CONDITIONS - IN-SITU HYBRIDIZATION AND IMMUNOCYTOCHEMICAL DETECTION

The expression of beta-amyloid precursor protein (beta APP) by astrocy tes is well documented; however, data concerning oligodendrocytes rema in controversial, The main goal of the present study was to determine whether or not oligodendrocytes in culture constitutively express the different beta APP isoforms, Oligodendrocytes were cultured in a chemi cally defined medium that avoids putative effects of unknown serum fac tors on oligodendrocyte development, We have employed immunocytochemis try and in situ hybridization with antibodies and synthetic oligonucle otides recognizing, respectively, specific protein epitopes and mRNA t ranscripts of rat beta APP isoforms, Oligodendrocytes, in both mixed p rimary cultures in the presence of serum or in secondary cultures in d efined medium, were clearly labeled by antibodies directed to differen t beta APP sequences, Antibodies against the serine protease inhibitor domain of beta APP, also strongly labelled oligodendrocytes. Immunohi stochemistry and in situ hybridization were combined to determine prec isely the expression of different isoforms of beta APP. In situ hybrid ization revealed the presence in oligodendrocytes of mRNA transcripts coding not only for beta APP(695) but also for beta APP(770) and beta APP(751). This indicates that beta APP immunoreactivity found in oligo dendrocytes corresponds to constitutive expression of beta APP. Oligod endrocyte cultured in chemically defined medium are able to express no t only beta APP(695) but also beta APP(770), beta APP(751) isoforms co ntaining the Kunitz protease inhibitor domain, Although the role of be ta APP in the pathological processes of Alzheimer's disease (AD) remai ns unknown, possible disturbances of beta APP processing and/or synthe sis in oligodendrocytes may account for some myelin disorders observed in AD and other senile dementias. (C) 1997 Wiley-Liss, Inc.