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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
APP
Volume 270,
Number 20,
Issue of May 19, pp. 11839-11844, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
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.
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