Cardiff University School of Medicine Science Seminar Series

Michael Heneka has been the director of the Luxembourg Centre for Systems Biomedicine at the University of Luxembourg since 2021. He is a board-certified neurologist and clinician-scientist with over 25 years of experience in studying neurodegenerative diseases at experimental, preclinical and clinical levels. At the clinical level, he established a neurodegenerative outpatient unit at both the University of Münster and the University of Bonn. From 2016 to 2021, he led the department of Neurodegenerative Disease and Geriatric Psychiatry in Bonn. He is further adjunct professor at the University of Massachusetts Chan Medical School and at the University of Bonn.

The Michael Heneka laboratory studies the interaction between the innate and adaptive immunity and the central nervous system. Inflammatory changes represent a common hallmark in neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), fronto-temporal dementia (FTD) and Alzheimer’s disease (AD).

Innate Immunity in Alzheimer’s disease

The accumulation of neurotoxic amyloid beta peptides along with neurofibrillary tangle formation are key pathological hallmarks of AD. The brain has been considered as an immune-privileged organ, however, increasing evidence from translational, genetic, and pathological studies suggests that activation of distinct innate immune pathways represent a third important disease component. Within several immune pathways, sustained NLRP3 inflammasome activation causes cognitive dysfunction and neurodegeneration but also a hyperinflammatory microglial cell death (pyroptosis) which leads to the release of activated inflammasome complexes called ASC specks, which may be accountable for the spread of AD pathology. Increased microglial cell death in turn will cause proliferation of microglial cells generating several subpopulations over time, which show functional and transcriptional changes compared to non-proliferating cells. Thus, while protective in early stages, the ongoing and chronic microglial activation actively drives AD phenotypes and pathology, offering new and yet unused opportunities for therapeutic interventions.