Expression of CD74 is increased in neurofibrillary tangles in Alzheimer's disease

Kathryn J. Bryan, Xiongwei Zhu, Peggy L. Harris, George Perry, Rudy J. Castellani, Mark A. Smith, Gemma Casadesus*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by progressive memory loss. Pathological markers of AD include neurofibrillary tangles, accumulation of amyloid-β plaques, neuronal loss, and inflammation. The exact events that lead to the neuronal dysfunction and loss are not completely understood. However, pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor α, are increased in AD, along with gene expression of major histocompatibility complex (MHC) class II molecules and macrophage migration inhibitory factor (MIF). MHC class II molecules are found in microglia of the brain, while MIF is found in both microglia and neurons of the hypothalamus, hippocampus, and cortex. MIF is not only a lymphocyte mediator but also a pituitary factor with endocrine properties and can mediate phosphorylation of the extracellular signal-regulated kinase-1/2 MAP kinases pathway. In this study, we looked at CD74, an integral membrane protein that acts as both a chaperone for MHC class II molecules as well as a receptor binding site for MIF. CD74 was recently found to be increased in microglia in AD cases compared to age-matched controls, but has not been reported in neurons. In our analysis, immunohistochemistry revealed a significant increase in CD74 primarily in neurofibrillary tangles, amyloid-β plaques, and microglia. This is the first finding to our knowledge that CD74 is increased in neurons of AD cases compared to age-matched control cases.

Original languageEnglish (US)
Article number13
JournalMolecular neurodegeneration
Volume3
Issue number1
DOIs
StatePublished - 2008
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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