Expression of CD74 is increased in neurofibrillary tangles in Alzheimers diseaseReport as inadecuate




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Molecular Neurodegeneration

, 3:13

First Online: 11 September 2008Received: 20 March 2008Accepted: 11 September 2008

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.

List of abbreviationsADAlzheimer disease

Aβamyloid-β

DAB3,3-diaminobenzidine

ERKextracellular-regulated-kinase

IL-1βinterleukin-1β

IL-6interleukin-6

KSPlysine-serine-proline

MIFmacrophage migration inhibitory factor

MHCmajor histocompatibility complex

MMSEmini-mental state exam

NFTneurofibrillary tangles

PGE2prostaglandin E2

TBSTris-buffered saline, TNFα: tumor necrosis factor α.

Electronic supplementary materialThe online version of this article doi:10.1186-1750-1326-3-13 contains supplementary material, which is available to authorized users.

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Author: Kathryn J Bryan - Xiongwei Zhu - Peggy L Harris - George Perry - Rudy J Castellani - Mark A Smith - Gemma Casadesus

Source: https://link.springer.com/







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