Neuroinflammation

Prof. Dr. Michael T. Heneka

Areas of investigation/research focus

Neuroinflammation is a common hallmark in e.g. amyotrophic lateral sclerosis (ALS), fronto-temporal dementia (FTD) and Alzheimer’s disease (AD). AD is characterized by the accumulation of extracellular amyloid-beta (Aβ) in amyloid plaques and intracellular tau in neurofibrillary tangles (NFTs).

Activation of microglia, the innate immune cells of the brain, seems to be involved in the development and progression of these pathologies in AD but also plays a role in other neurodegenerative diseases. To date, the underlying mechanisms in the transition of an initially protective to a chronic, harmful neuroinflammatory response are unknown.

Our basic laboratory research aims at understanding molecular mechanisms of inflammatory regulation in a variety of neurodegenerative disease by using for example novel preclinical mouse models and state-of-the-art techniques like two-photon imaging, transcriptome analysis and induced pluripotent stem cells (iPSCs).

Current clinical research is focused on various aspects of neuroinflammation involved in neurodegenerative and cerebrovascular diseases with the goal of developing new biomarkers and medical intervention programs.

1. Neuroinflammation can transit from a beneficial to a detrimental response. We aim to identify gene network hubs in proliferative microglia that mark key steps of this transition in order to find points of intervention. (TracInflam project, supported by ERA-NET NEURON)

2. Genome-wide association studies have linked the immune receptor TREM2 to AD. To shed light on the mechanistic link, we analyze the role of different TREM2 variants in the microglial Aβ uptake in a longitudinal study in AD mouse models. (PHAGO project, supported by IMI_JU)

3. Activation of the NLRP3 inflammasome in microglia seems to play an important role in AD. We use in vitro and in vivo models to determine the contribution of the inflammasome in the progression of microglia activation, neuroinflammation and AD pathology. (InCure project, supported by JPND)

4. Tau accumulation is another hallmark of AD, but the role of neuroinflammatory events in the development of tau pathology remains elusive. We analyze the impact of the NLRP3 inflammasome on tau accumulation and the role of microglia as a potential link between Aβ and tau pathology.

5. Human cellular models are important tools to find efficient therapies for neurodegenerative diseases. We focus our efforts on the generation of microglia-like cells from patient-derived iPSCs, which we use to investigate the role of the nuclear receptor PPARγ in the neuroinflammatory response. (MADGIC project, supported by JPND)

6. Our biomarker program translates basic research findings into clinical diagnostics. The program is based on the well-characterized AD amyloid and tau biomarkers but also investigates the applicability of inflammatory markers in discrimination of patients in different stages of the disease.

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