Macrophage migration inhibitory factor and neuroinflammation in early Alzheimer's Disease

• Applicant: Professor Dr. Michael Bacher
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2012 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 222177571

Systemic and cerebral inflammatory processes are common in Alzheimer's disease (AD), however, the pathomechanisms linking inflammatory processes to AD pathology are not well understood, and it is not known whether inflammation accelerates clinical disease progression. The macrophage migration inhibitory factor (MIF) plays a central regulatory role in the innate immune response. There is first evidence that MIF up-regulation may trigger cerebral inflammation in AD, and contribute to amyloid production and neurodegeneration. The project includes in vitro and animal studies to address hypotheses of causal relationships between inflammatory processes, cerebral pathology, and cognition as well as observational studies in patients with pre-dementia and mild dementia due to AD to verify these hypotheses in humans. Using a specific MIF inhibitor, the experimental studies will evaluate MIF effects on cytokine expression, amyloid production, and toxicity as well as the relationships between MIF-mediated inflammation, cognitive performance, and cerebral pathology at different disease stages in transgenic APP mice. The clinical part aims at determining whether inflammation is increased in patients with very early AD, whether it is associated with markers of amyloid pathology and neurodegeneration, and whether increased inflammatory activity accelerates cognitive and functional deterioration. This project may add detailed evidence for the involvement of inflammatory processes in very early AD pathology, and for a central role of MIF in triggering these processes. Evidence that inflammation related to AD pathology accelerates clinical disease progression may open new perspectives of anti-inflammatory drug use in early AD.

• DFG Programme: Research Grants
• International Connection: Switzerland
• Participating Person: Professor Dr. Julius Popp