Neuroinflammation and Neurodegeneration

September 25-October 2, 2027

Director: Soyon Hong

UK Dementia Research Institute, University College London, UK

Co-Director: Bart De Strooper

UK Dementia Research Institute, University College London, UK & KU Leuven, Belgium

Faculty:

Florent Ginhoux, Gustave Roussy, Villejuif, France

Joachim Herz, UT Southwestern Medical Center, Dallas, USA

Baljit Khakh, UK Dementia Research Institute, Cardiff University, UK

Andrew Yang, Gladstone Institutes & University of California, San Francisco, USA

Sonia Garel, Collège de France & École Normale Supérieure (IBENS), Paris, France

Soyon Hong, UK Dementia Research Institute, University College London, UK

Bart De Strooper, UK Dementia Research Institute, University College London, UK & KU Leuven, Belgium

It is increasingly clear that neurodegeneration cannot be understood by considering neurons in isolation. The nervous system is shaped by continuous communication between neurons, glial cells and immune cells, both within the CNS and across its borders. Microglia and astrocytes regulate synaptic function, neuronal activity, tissue homeostasis and responses to injury; oligodendrocytes and myelin are increasingly implicated in disease vulnerability and repair; and neuronal signals themselves shape local immune and glial states. At the same time, emerging work highlights important contributions from brain-border and peripheral immune populations, revealing neurodegeneration as a systems-level disorder of cellular communication.

Understanding when these responses are protective, adaptive or ultimately detrimental remains a major challenge. Their effects vary across ageing, anatomical compartments and stages of disease, and the same cellular pathways can have markedly different consequences depending on context. Defining how neurons, glia and immune cells communicate—and how these interactions become dysregulated—will therefore be essential both for understanding disease mechanisms and for identifying new therapeutic opportunities.

The Faculty will bring leading expertise spanning neuronal, glial and immune biology in health and neurodegeneration. The Advanced Course will examine microglia and macrophages, astrocytes, oligodendrocytes and myelin, neuronal and synaptic biology, and peripheral and brain-border immunity. Particular emphasis will be placed on how these cellular systems interact to regulate neural function and homeostasis across development, ageing and disease, and how emerging mechanistic insights can be translated into new ways of thinking about neurodegenerative disorders.

Bart De Strooper

Inflection points and transitions in Alzheimer’s disease

Alzheimer’s disease is widely depicted as a linear cascade from amyloid-β accumulation to Tau pathology and neurodegeneration. We propose instead that the disease unfolds through discrete molecular, cellular and network phases organized around biological inflection points. At these thresholds, stress-driven loss of homeostasis produces qualitative shifts in cellular behavior that alter disease progression. These altered states spread across local tissue domains, accumulate as a mosaic across the brain, and progressively engage vulnerable centres of information processing that control cognitive performance. The induction of amyloid-associated Tau phosphorylation marks a pivotal inflection point, separating amyloid-dominated tissue states from domains in which neuronal Tau stress responses have emerged. This framework helps reconcile the dissociation between pathology and symptoms, clarifies the shared architecture of familial and sporadic disease and reframes Alzheimer’s disease as a disorder shaped by biological thresholds, timing, and progressive erosion of homeostatic resilience.

Florent Ginhoux

Microglia and brain macrophages in development and neurodegeneration

Microglia and brain-associated macrophages are essential regulators of brain development, homeostasis, and responses to injury. Beyond their classical immune functions, these cells shape neural circuits through synaptic remodelling, regulate neuronal and glial differentiation, and maintain tissue integrity through interactions with the neurovascular and immune systems. Developmental programs, especially in microglia, and signals from the local brain microenvironment govern their functions. However, during aging and neurodegenerative diseases, these regulatory networks can become disrupted, leading to persistent inflammation, altered cellular metabolism, impaired tissue repair, and neuronal dysfunction. Our research program aims to elucidate the molecular and cellular mechanisms controlling the diversity, plasticity, and functional specialization of microglia and brain-associated macrophages across development, aging, and neurodegeneration. By integrating advanced genomic approaches, experimental models, and translational research, including microglia-containing iPSC-derived brain organoids, we aim to uncover fundamental mechanisms of brain immunity and identify new therapeutic opportunities to preserve neural function and combat neurodegenerative diseases.