Co‐localization of Glia Maturation Factor and Progranulin in the Human Alzheimer's Disease Brains

Abstract

Amyloid plaques (APs) and neurofibrillary tangles (NFTs) are two major neuropathological hallmarks observed in the brains of Alzheimer's disease (AD) patients. Inflammatory mediators released from the activated glial cells and neurons induce neuroinflammation and neurodegeneration thereby exacerbating AD pathogenesis. We have previously shown that glia maturation factor (GMF), a proinflammatory brain protein is upregulated in the brains of AD patients. Additionally, we also found that the upregulated GMF is associated with APs and NFTs in the brains of AD patients. Progranulin a pleiotropic protein that serves as a precursor of active granulin peptides was also shown to be upregulated in the brains of AD patients. However, the association between GMF and progranulin has not yet been studied in the context of neurodegenerative diseases including AD. We analyzed frozen sections of temporal lobe from human AD patients in this study. Here, we investigated whether the upregulated GMF expression is associated with a corresponding increase in progranulin expression in the vicinity of APs in the AD brains using single and double immunohistochemistry and immunofluorescence staining. Our results show that progranulin immunoreactive neurons and activated microglia are present in the temporal cortex region of AD brains. We report increased progranulin and GMF expression in the vicinity of APs. Further, we also report significantly more progranulin expression in the neurons and glial cells in the brains of AD patients. Our data suggest that the increased expression of GMF and progranulin may synergize to play a critical role in neuroinflammation and neurodegeneration thereby exacerbating AD pathogenesis.Support or Funding InformationThis work was supported by the Veterans' Affairs Merit Award I01BX002477 and the National Institutes of Health Grants AG048205 and NS073670 to AZThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.