Co-Expression of Glia Maturation Factor and Apolipoprotein E4 in Alzheimer's Disease Brain

Apolipoprotein E4 (ApoE4) is a major genetic risk factor for Alzheimer’s disease (AD). The E4 allele of ApoE plays a crucial role in the inflammatory and neurodegenerative processes associated with AD. This is evident from the multiple effects of the ApoE isoforms in beta amyloid (Aβ) aggregation. Glia maturation factor (GMF) is a brain-specific neuroinflammatory protein, that we have previously demonstrated to be significantly upregulated in various regions of AD brains compared to non-AD control brains and that it induces neurodegeneration. We have previously reported that GMF is predominantly expressed in the reactive astrocytes surrounding APs in AD brain. In the present study, using immunohistochemical staining methods we show the expression of GMF and ApoE4 in AD brains. Double immunofluorescence labelling of GMF and ApoE4 showed their co-localization in the amyloid plaques (APs) of AD brain. We show the co-localization of GMF and ApoE4 in APs of AD brain by double immunohistochemical and dual immunofluorescence methods. Our results show that ApoE4 is present in APs of AD brain. Double immunofluorescence labelling method shows the relationship between ApoE4 and GMF expression in the APs in the AD brain. We found that GMF and ApoE4 were strongly expressed and co-associated in APs and in the reactive astrocytes surrounding APs in AD. The increased expression of GMF in APs and neurofibrillary tangles (NFTs) in the AD brain, and the co-localization of GMF and ApoE4 in APs suggest that GMF and ApoE4 together should be contributing to the pathogenesis of AD.