THE ALZHEIMER AMYLOID PRECURSOR PROTEOGLYCAN (APPICAN) IS PRESENT IN BRAIN AND IS PRODUCED BY ASTROCYTES BUT NOT BY NEURONS IN PRIMARY NEURAL CULTURES

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 ent 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 APP(695) 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.