Recent studies showed that the Alzheimer
amyloid precursor (APP) occurs as the core
protein of a
chondroitin sulfate proteoglycan (
appican) in C6
glioma cells. In the present study we show that
appican is present in both human and rat brain tissue. Cortical rat brain cell cultures were used to identify
appican-producing cells. Soluble secreted and cell-associated
appican was produced by mixed glial cultures but not by primary neuronal cultures. Among the three major glial cell types, astrocytes produced high levels of
appican, while oligodendrocytes failed to produce any. Only low levels of this molecule were occasionally detected in microglial cultures. Expression of
appican in astrocyte cultures was regulated by the composition of the growth media. N2a
neuroblastoma cells also produced
appican; however, treatment with dibutyryl cAMP which promotes neuronal differentiation in these cells inhibited its production without inhibiting synthesis of APP. In contrast to the restricted expression of
appican, APP was present in all cultures, and its production was independent of
appican synthesis. Neuronal cultures produced mainly APP695 while glial cultures produced the Kunitz type
protease inhibitor containing APP. The astrocyte-specific expression of
appican suggests a function distinct from the function of APP. Brain appicans may play a role in the development of
Alzheimer disease neuropathology.