THE ALZHEIMERS AMYLOID PRECURSOR PROTEIN IS PRODUCED BY TYPE-I ASTROCYTES IN PRIMARY CULTURES OF RAT NEUROGLIA

The production of β‐amyloid precursor protein (βAPP) by primary mixed glial cell cultures from cerebral cortex of 2–3 day postnatal rats was examined by Northern and Western blotting and by immunocytochemistry. A single 3.5 kb βAPP RNA transcript was detected using probes recognizing all forms of βAPP messenger RNA. No signal was detected with a probe specific for the alternately spliced Kuntiz protease inhibtor (KPI) region. In Western blot analysis of protein extracts, antisera specific for either the cytoplasmic or extracellular part of βAPP detected several proteins ranging from 105 to 140 kDa. None of these were recognized by an antiserum specific to the KPI insert of the βAPP. Multicolor immunofluorescence showed βAPP. immunoreactivity in type I (GFAP+A2B5−) astrocytes, distributed in a fibrillar pattern like that of glial fibrillary acidic protein (GFAP). No βAPP immunoreactivity was detected in oligodendrocytes (GC+) or in A2B5+ progenitor cells. Moreover, no cultured cells showed immunostaining with an antiserum specific for the KPI sequence of βAPP. We conclude that type I astrocytes in primary culture produce amyloid precursor, but that oligodendrocytes and their precursors do not. Moreover, type I astrocytes produce predominently the βAPP subtypes which lacks the KPI sequence. Copyright © 1990 Wiley‐Liss, Inc.