We have previously demonstrated that Glia maturation factor (GMF), a brain‐specific protein isolated, sequenced and cloned in our laboratory, is a prominent mediator of inflammation in CNS leading to the death of neurons. In the present study we demonstrate, for the first time, a significant up regulation of the GMF in AD brain compared to age matched ND (non‐demented) controls. We analyzed brain regions by ELISA using specific anti‐GMF antibodies developed and characterized in our laboratory. We observed a significant increase in GMF concentration in entorhinal cortex, parietal cortex, frontal cortex, occipital cortex, perirhinal cortex, and temporal cortex of AD brain. The association between augmented expression of GMF and APs/NFTs in AD was also evaluated. Double immunofluorescence labeling for GMF and APs show strongly GMF‐positive cells with neuron and glia morphology are co‐localized with APs and NFTs. The astrocytes adjacent to the APs display ramified processes and express GMF and GFAP, indicative of an activated phenotype associated with inflammation. Our results provide strong evidence that under conditions of neuro degeneration in AD, the expression of GMF is significantly upregulated. These results imply that augmented expression of GMF is associated with AD pathology.(Supported by VA Merit Review award and NIH/NINDS grant NS‐47145)