ASTROCYTE-APOLIPOPROTEIN-E ASSOCIATIONS IN SENILE PLAQUES IN ALZHEIMER-DISEASE AND VASCULAR-LESIONS - A REGIONAL IMMUNOHISTOCHEMICAL STUDY

While apolipoprotein E (ApoE) and beta-amyloid (AP) co-localize in sen ile plaques in cortex and cerebellum in Alzheimer disease (AD), the A beta-positive, predominantly diffuse plaques in the striatum do not ex hibit ApoE immunoreactivity regardless of disease duration. As astrocy tes are a major source of ApoE in the brain, we investigated potential regional differences in the ability of astrocytes to produce ApoE tha t 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 suba cute and old infarcts in both AD and non-AD cases. We found GFAP and A poE immunoreactivity, but not A beta label. in cell bodies and process es of reactive astrocytes in zones of infarction within cerebral corte x, striatum, and cerebellum, indicating that astrocytes are capable of upregulating ApoE within these 3 regions. In contrast, while astrocyt es surrounded many neocortical neuritic plaques in AD, these GFAP-posi tive cells failed to label with ApoE; instead, ApoE label within plaqu es paralleled that of A beta. As expected, neither the ApoE-negative d iffuse plaques of the striatum nor the ApoE-immunopositive diffuse pla ques of the cerebellum were clearly associated with GFAP-immunoreactiv e astrocytes. The apparent absence of ApoE label in cortical plaque-as sociated astrocytes may signify a regulatory mechanism affecting ApoE synthesis and secretion, influenced by binding of ApoE to fibrillar am yloid within the plaques, neuritic changes, or other factors.