Increase of adenomatous polyposis coli immunoreactivity is a marker of reactive astrocytes in Alzheimer's disease and in other pathological conditions

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are responsible for colon cancer in familial adenomatous polyposis coli and in many sporadic colorectal tumors. The product of the A-PC gene is also esse ntial for normal development and is expressed in the adult brain. We have i nvestigated the immunocytochemical localization of APC in the temporal cort ex and hippocampus of normal human brain, in Alzheimer's disease (AD) and i n several other neuropathological conditions. APC was expressed in neuronal cell bodies and dendrites both in control subjects and in patients with di fferent diseases. In addition, a high APC expression was observed in a prop ortion of fibrillary and glial fibrillary acidic protein-positive astrocyte s in AD. Furthermore, in AD the proportion of APC-positive astrocytes was h igher in astrocytes associated with P-amyloid (AP) deposits in senile plaqu es than in astrocytes not associated to AP deposits. APC-positive astrocyte s were also observed in control cases, in diffuse Lewy body disease, in Cre utzfeldt-Jacob disease, in HIV encephalitis and around cerebral infarcts. T umoral astrocytes in pilocytic astrocytoma and in glioblastoma were also st rongly A-PC positive. APC was not detected in cultured astroglial cells. Th ese results indicate that A-PC expression is upregulated in astrocytes foll owing their activation by several types of pathological insults and is a ne wly identified molecular characteristic of the reactive phenotype of astroc ytes, possibly related to the control of cell proliferation. In addition, i t also suggests that AP, and/or the inflammatory process associated with AP deposits, is responsible for a preferential increase of A-PC expression in astrocytes in AD.