Neuroinflammation and Neurodegeneration
September 27 – October 4, 2025
Director: Soyon Hong
UK Dementia Research Institute at University College London
Co-Director: Bart de Strooper
UK Dementia Research Institute at University College London, London, UK & KU Leuven, Belgium
Faculty:
Baljit Khakh, University of California, Los Angeles, USA
Florent Ginhoux, Gustave Roussy Campus, Paris, France
Sonia Garel, École Normale Superieure, Paris, France
Costantino Iadecola, Weill Cornell Medical College, New York, USA
Klaus Nave, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
Thora Karadottir, Cambridge University, UK
It is becoming increasingly clear that neuroimmune mechanisms critically contribute to neurodegeneration. Neuroglial interactions involving microglia and astrocytes govern proper synaptic function, synchronize clearance of toxic aggregates, and coordinate neuroinflammation. Oligodendrocytes and white matter alterations are observed. Furthermore, emerging data raise a crucial role for peripheral-central immune crosstalk in neurodegeneration. How the different non-neuronal cells contribute to neurodegeneration remains, however, elusive. Therapeutic-wise, there is the grand challenge of balancing the positive and negative consequences of these cellular reactions across ageing and brain borders. Thus, deep insight into how various cells work together to resolve neuroinflammation and mediate neuronal health will be necessary to ultimately change the prognosis of neurodegeneration.
The Faculty will bring leading expertise and insight into neuro-glia-immune mechanisms in neurodegeneration. The Advanced Course will delve into the roles of microglia, astrocytes and OPCs in health and pathology and how brain’s various cell types work together to modulate neuronal function and homeostasis in health (development and adult) and distinct disease states.
Costantino Iadecola
Neuroimmune mechanisms, vascular damage and Alzheimer’s disease
A growing body of evidence suggests that neurovascular damage plays a significant role in Alzheimer’s disease (AD), the leading cause of age-related dementia. This lecture will explore how AD pathology and related risk factors, such as ApoE4 carriage and high blood pressure, impair microvascular function, contributing to cognitive decline. The focus will be on neuroimmune mechanisms, with particular emphasis on the emerging role of border-associated macrophages—brain-resident innate immune cells distinct from microglia—in AD pathology, hypertension, and ApoE4. Finally, the implications of these neurovascular and neuroimmune effects for ARIA syndrome, a treatment-limiting and potentially fatal complication of Aβ immunotherapy, will be discussed.
Bart De Strooper
Amyloid plaques are one of the defining pathologies in Alzheimer’s disease and trigger a long cellular phase which gradually leads to Tau pathology, neuronal dysfunction, granulovacuolar neurodegeneration and necroptosis of neurons. This neurocentric view of the disease is too narrow. Very early on in the disease, a coordinated astro- and microglia response is observed, which actively modulates the disease process. I will explain how this view is gradually taking centre stage in our thinking about this disorder that affects millions worldwide.
Thora Karadottir
From lesion to recovery: Myelin’s role in neuroinflammation
Half of the human brain is white matter. Its function relies on oligodendrocytes producing myelin to support neuronal function and enable fast communication between neurons. Myelin is essential for both cognitive and motor function, and changes in myelin are increasingly recognised as a mechanism for learning. The importance of myelin is particularly evident in diseases such as multiple sclerosis, where myelin damage leads to cognitive and motor disabilities. Furthermore, recent studies have underscored the role of myelin in conditions previously considered purely neuronal, such as dementia.
Throughout life, oligodendrocyte precursor cells (OPCs) differentiate into myelin-forming oligodendrocytes and remain the principal proliferative cell population in the adult brain. OPCs are capable of sensing neuronal activity through synaptic inputs, voltage-gated ion channels, and neurotransmitter receptors, and they differentiate into myelinating oligodendrocytes in response to changes in neuronal activity. In young adults, OPCs respond effectively to both activity and demyelinating lesions, regenerating lost myelin and restoring function. However, with normal ageing, both myelin maintenance and regenerative capacity decline. The primary cause of regenerative failure is thought to be the reduced ability of OPCs to differentiate into new myelinating oligodendrocytes.
This lecture will explore the mechanisms underlying activity-dependent myelination and discuss how neuronal activity can both promote and impair myelin regeneration. It will also address the consequences of focal white matter lesions on neuronal circuit function and neuroinflammation, introducing a novel perspective on how grey matter neuroinflammation regulates myelin regeneration—and how restoring myelin can, in turn, resolve inflammation and support functional recovery.
Soyon Hong
Microglia are critical contributors to synapse function and health. One important question is how microglia detect and determine which synapses to eliminate and which ones to spare. Emerging data suggest that microglial cell states, including the synapse phagocytosing ones, are influenced not only by changes in neuronal activity but also by surrounding astrocytes and perivascular macrophages. Further, cell-cell crosstalk influencing synaptic fate can also involve adaptive immune signalling along brain borders. I will discuss various potential modulators of microglia-synapse interactions and the consequences of these processes in disease.
Florent Ginhoux
Brain macrophage heterogeneity
Brain macrophages include microglia in the parenchyma, border-associated macrophages in the meningeal-choroid plexus-perivascular space, and monocyte-derived macrophages that infiltrate the brain under various disease conditions. The vast heterogeneity of these cells has been elucidated over the last decade using revolutionary multi-omics technologies. As such, we can now start to define these various macrophage populations according to their ontogeny and diverse functional programs during brain development, homeostasis, and disease pathogenesis. During the lectures, I will first outline the critical roles played by brain macrophages during development and healthy ageing. I will then discuss how brain macrophages might undergo reprogramming and contribute to neurodegenerative disorders, autoimmune diseases, and glioma. Finally, I will speculate about the most recent and ongoing discoveries prompting translational attempts to leverage brain macrophages as prognostic markers or therapeutic targets for diseases that affect the brain.
Klaus Nave
Oligodendrocytes in Health and Disease: From Myelin Function to Neurodegeneration
The lectures will cover recent progress in myelin biology and explore the multifaceted roles of oligodendrocytes in CNS function and pathology, using the tools of mouse genetics, transcriptomics, and advanced imaging approaches. Once considered passive support cells, oligodendrocytes are now recognized as key players in maintaining axonal integrity, brain energy metabolism, modulators of immune responses, and contributing to pathological processes such as amyloid deposition. We will examine how aging and myelin dysfunction accelerate Alzheimer’s disease progression, how oligodendrocytes themselves contribute to amyloid-β production, and how myelin insulation can paradoxically increase axonal vulnerability in inflammatory settings. During the Advanced Course, recent findings of ongoing myelin turnover and oligodendroglial fatty acid metabolism becoming a CNS energy reserve during metabolic stress will be highlighted.
Sonia Garel
Microglia in early brain development: a window of opportunity
Microglia, the main resident immune cells of the brain, are highly dynamic and responsive to their environment. Their capacity for cellular and transcriptomic change is especially evident during development but also features prominently in ageing and neurodegenerative diseases. These lectures will explore how early brain development offers a unique opportunity to understand microglial biology. As they begin to colonize the brain during embryogenesis, microglia rapidly become the most abundant glial population, placing them in a key position to influence brain organization at a time when other glial cells are still emerging. We will present published and unpublished work revealing how microglia contribute to the construction and maintenance of the developing brain, and how some of their early states mirror those observed in neurodegenerative conditions. By focusing on development, this lecture aims to highlight both the specificities of this time window and its relevance for understanding broader principles of microglial function in health and disease.
Baljit S. Khakh
Astrocytes in neural circuits
Astrocytes are a numerous type of glial cell. Baljit Khakh (Bal) will present three lectures to get everyone up to speed on the latest work on astrocytes, astrocyte-neuron interactions and functions of astrocytes in neural circuits. Lecture 1 will provide basic background material on astrocytes and delve into their core functions. Lecture 2 will explore astrocyte-neuron interactions with a focus on astrocyte calcium signaling. Lecture 3 will explore astrocyte diversity and the functions of a molecularly defined astrocyte subset for a specific neural circuit. Throughout the lectures, emphasis will be placed on rigorous work to provide attendees with sufficient expertise to begin exploring astrocytes and astrocyte-neuron interactions in their own research. All three lectures are expected to involve multiple questions and lively discussions with the attendees.
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