Abstract
BackgroundMacrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine. Chronic inflammation induced by amyloid β proteins (Aβ) is one prominent neuropathological feature in Alzheimer’s disease (AD) brain.MethodsElisa, Western blot, and immunohistochemical staining analysis were performed to examine the level of MIF protein in CSF and brain tissues. MTT and LDH assays were used to examine the neurotoxicity, and the Morris Water Maze test was performed to examine the cognitive function in the MIF+/−/APP23 transgenic mice.ResultsMIF expression was upregulated in the brain of AD patients and AD model mice. Elevated MIF concentration was detected in the cerebrospinal fluid of AD patients but not in that of the patients suffering from mild cognitive impairment and vascular dementia. Reduced MIF expression impaired learning and memory in the AD model mice. MIF expression largely associates with Aβ deposits and microglia. The binding assay revealed a direct association between MIF and Aβ oligomers. Neurons instead of glial cells were responsible for the secretion of MIF upon stimulation by Aβ oligomers. In addition, overexpression of MIF significantly protected neuronal cells from Aβ-induced cytotoxicity.ConclusionOur study suggests that neuronal secretion of MIF may serve as a defense mechanism to compensate for declined cognitive function in AD, and increased MIF level could be a potential AD biomarker.
Highlights
Alzheimer’s disease (AD) is the most common cause of dementia
To assess the migration inhibitory factor (MIF) level in AD patients, Cerebrospinal fluid (CSF) was collected from control subjects and patients diagnosed with mild cognitive impairment (MCI) and AD
Our results showed that the MIF level in the CSF was significantly upregulated in the patients diagnosed with AD (14.62 ± 1.15 ng/ml) compared to the control subjects (10.07 ± 0.60 ng/ml)
Summary
Alzheimer’s disease (AD) is the most common cause of dementia. It is characterized by the intracellular neurofibrillary tangles, extracellular neuritic plaques, and neuronal loss. Extracellular neuritic plaques are the unique feature distinguishing AD from other forms of dementia and neurodegenerative diseases. Aβ deposits are potent in the activation of Macrophage migration inhibitory factor (MIF) is a pleiotropic protein that participates in many cellular activities and plays an essential role in regulating the inflammatory response, energy metabolism, and apoptosis. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine. Chronic inflammation induced by amyloid β proteins (Aβ) is one prominent neuropathological feature in Alzheimer’s disease (AD) brain
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
