Oligodendrocytes express different isoforms of β-amyloid precursor protein in chemically defined cell culture conditions: In situ hybridization and immunocytochemical detection

The expression of β-amyloid precursor protein (βAPP) by astrocytes is well documented; however, data concerning oligodendrocytes remain controversial. The main goal of the present study was to determine whether or not oligodendrocytes in culture constitutively express the different βAPP isoforms. Oligodendrocytes were cultured in a chemically defined medium that avoids putative effects of unknown serum factors on oligodendrocyte development. We have employed immunocytochemistry and in situ hybridization with antibodies and synthetic oligonucleotides recognizing, respectively, specific protein epitopes and mRNA transcripts of rat βAPP isoforms. Oligodendrocytes, in both mixed primary cultures in the presence of serum or in secondary cultures in defined medium, were clearly labeled by antibodies directed to different βAPP sequences. Antibodies against the serine protease inhibitor domain of βAPP, also strongly labelled oligodendrocytes. Immunohistochemistry and in situ hybridization were combined to determine precisely the expression of different isoforms of βAPP. In situ hybridization revealed the presence in oligodendrocytes of mRNA transcripts coding not only for βAPP695 but also for βAPP770and βAPP751. This indicates that βAPP immunoreactivity found in oligodendrocytes corresponds to constitutive expression of βAPP. Oligodendrocyte cultured in chemically defined medium are able to express not only βAPP695 but also βAPP770, βAPP751 isoforms containing the Kunitz protease inhibitor domain. Although the role of βAPP in the pathological processes of Alzheimer's disease (AD) remains unknown, possible disturbances of βAPP processing and/or synthesis in oligodendrocytes may account for some myelin disorders observed in AD and other senile dementias. J. Neurosci. Res. 50:50–61, 1997. © 1997 Wiley-Liss, Inc.