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 APC gene is also essential for normal development and is expressed in the adult brain. We have investigated the immunocytochemical localization of APC in the temporal cortex and hippocampus of normal human brain, in Alzheimer's disease (AD) and in several other neuropathological conditions. APC was expressed in neuronal cell bodies and dendrites both in control subjects and in patients with different diseases. In addition, a high APC expression was observed in a proportion of fibrillary and glial fibrillary acidic protein-positive astrocytes in AD. Furthermore, in AD the proportion of APC-positive astrocytes was higher in astrocytes associated with beta-amyloid (Abeta) deposits in senile plaques than in astrocytes not associated to Abeta deposits. APC-positive astrocytes were also observed in control cases, in diffuse Lewy body disease, in Creutzfeldt-Jacob disease, in HIV encephalitis and around cerebral infarcts. Tumoral astrocytes in pilocytic astrocytoma and in glioblastoma were also strongly APC positive. APC was not detected in cultured astroglial cells. These results indicate that APC expression is upregulated in astrocytes following their activation by several types of pathological insults and is a newly identified molecular characteristic of the reactive phenotype of astrocytes, possibly related to the control of cell proliferation. In addition, it also suggests that Abeta, and/or the inflammatory process associated with Abeta deposits, is responsible for a preferential increase of APC expression in astrocytes in AD.
Leroy
K
K
Laboratory of Histology, Neuroanatomy and Neuropathology, School of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Duyckaerts
C
C
Bovekamp
L
L
Müller
O
O
Anderton
B H
BH
Brion
J P
JP
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D051381:Rats; D014018:Tissue Distribution
D025601:Adenomatous Polyposis Coli Protein