Astrocyte-apolipoprotein E associations in senile plaques in Alzheimer disease and vascular lesions: a regional immunohistochemical study.
While apolipoprotein E (ApoE) and beta-amyloid (A beta) co-localize in senile plaques in cortex and cerebellum in Alzheimer disease (AD), the A beta-positive, predominantly diffuse plaques in the striatum do not exhibit ApoE immunoreactivity regardless of disease duration. As astrocytes are a major source of ApoE in the brain, we investigated potential regional differences in the ability of astrocytes to produce ApoE that might affect A beta processing and the progression of AD pathology. Using antibodies to ApoE, glial fibrillary acidic protein (GFAP), and A beta, we compared the pattern of immunoreactivity in senile plaques in AD autopsy tissue with that of reactive astrocytes surrounding subacute and old infarcts in both AD and non-AD cases. We found GFAP and ApoE immunoreactivity, but not A beta label in cell bodies and processes of reactive astrocytes in zones of infarction within cerebral cortex, striatum, and cerebellum, indicating that astrocytes are capable of upregulating ApoE within these 3 regions. In contrast, while astrocytes surrounded many neocortical neuritic plaques in AD, these GFAP-positive cells failed to label with ApoE; instead. ApoE label within plaques paralleled that of A beta. As expected, neither the ApoE-negative diffuse plaques of the striatum nor the ApoE-immunopositive diffuse plaques of the cerebellum were clearly associated with GFAP-immunoreactive astrocytes. The apparent absence of ApoE label in cortical plaque-associated astrocytes may signify a regulatory mechanism affecting ApoE synthesis and secretion, influenced by binding of ApoE to fibrillar amyloid within the plaques, neuritic changes, or other factors.
Shao
Y
Y
Department of Pathology & Laboratory Medicine, VA Medical Center, Decatur, GA 30033, USA.
Gearing
M
M
Mirra
S S
SS
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002544:Cerebral Infarction / Q000378:metabolism* / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D014018:Tissue Distribution
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D005904:Glial Fibrillary Acidic Protein