Print This PostThe complement system spent decades filed under innate immunity — a set of blood proteins that tag pathogens and punch holes in them. That filing is now looking badly out of date.
Complement proteins are made in the brain, they mark synapses for removal, and the genetics keep pointing back at them. What was once a footnote in neuroimmunology is turning into one of the more credible therapeutic targets in neurodegeneration.
This playlist brings together five talks recorded at the Complement and the Brain satellite symposium, held on Tuesday 1 September 2026 in Cardiff alongside the 20th European Meeting on Complement in Human Disease. The symposium was sponsored by the UK Dementia Research Institute, and set out to run from fundamental mechanisms through to therapeutic development — which is roughly the arc these recordings follow.
Professor Cynthia Lemere explores how activation of the complement system may contribute to amyloid-related imaging abnormalities (ARIA), a side effect of anti-amyloid antibody treatments for Alzheimer’s disease.
She presents preclinical research linking complement activation with vascular inflammation, blood–brain barrier leakage and microhaemorrhages. An engineered antibody that prevented C1q binding reduced microhaemorrhages by approximately 75%, suggesting a potential route towards safer treatments.
Professor Lemere is Professor of Neurology at Harvard Medical School and the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital in Boston. Her research focuses on harnessing the immune system to treat Alzheimer’s disease. Her laboratory investigates the role of immune proteins in Alzheimer’s, the clearance of amyloid-beta from the brain, and the development and progression of Alzheimer’s disease in people with Down syndrome.
Presented at the Complement and the Brain Satellite Symposium during the 20th European Meeting on Complement in Human Disease on Tuesday 1 September 2026 in Cardiff. Find out more about the event at: https://emchd2026.org/
#AlzheimersDisease #DementiaResearch #ComplementSystem
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Dementia Researcher works alongside events organisers to share their work. If you're organising a dementia research event and would like us to record or share your talks, to get them open access and to reach a wider audience, get in touch: https://www.dementiaresearcher.nihr.ac.uk
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Chapters
00:00 Introduction
00:58 Overview of the complement system
03:06 Complement in Alzheimer’s disease
06:25 Anti-amyloid antibodies and amyloid clearance
07:39 Understanding ARIA
10:59 How complement activation may cause ARIA
12:30 Mouse models and 3D6 treatment
17:12 Complement activation and microhaemorrhages
18:38 Immune-cell and molecular responses
21:28 Effects of prolonged antibody treatment
23:00 Evidence from human ARIA cases
23:49 Can blocking C1q reduce ARIA?
28:07 Conclusions
29:36 Acknowledgements
Professor Marcela Pekna examines how C3a receptor (C3aR) signalling influences brain repair and recovery after stroke.
She presents evidence from mouse studies suggesting that C3aR has different roles over time. Its absence may reduce damage during the acute phase but later limit neuroplasticity and worsen secondary neurodegeneration. Intranasal C3a treatment, started one week after stroke, improved motor recovery, reduced astrocyte reactivity and supported synaptic plasticity and structural brain connectivity.
Marcela Pekna is Professor of Neuroimmunology at the University of Gothenburg, where she leads the Regenerative Neuroimmunology research group. Her research explores interactions between the immune system and brain, focusing on stroke, neuroinflammation, astrocyte biology and brain repair. Her work aims to develop treatments that promote recovery and regeneration following neurological injury and disease.
Presented at the Complement and the Brain Satellite Symposium during the 20th European Meeting on Complement in Human Disease on Tuesday 1 September 2026 in Cardiff. Find out more about the event at: https://emchd2026.org/
#DementiaResearch #ComplementSystem #StrokeResearch #Neuroimmunology
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Dementia Researcher works alongside events organisers to share their work. If you're organising a dementia research event and would like us to record or share your talks, to get them open access and to reach a wider audience, get in touch: https://www.dementiaresearcher.nihr.ac.uk
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Chapters
00:00 Introduction
00:46 Stroke burden and long-term disability
02:35 Ischaemic and haemorrhagic stroke
04:03 The C3a receptor in the brain
04:50 Lessons from C3aR knockout mice
07:12 Intranasal C3a as a recovery treatment
08:27 Astrocytes and gene-expression changes
11:53 Neuroplasticity and synaptic recovery
13:59 Structural brain connectivity
15:00 C3a treatment after haemorrhagic stroke
16:39 Neurodegeneration beyond the stroke lesion
18:16 Complement activation in the thalamus
21:24 Neuroimaging effects of intranasal C3a
24:12 Inflammation, C1q and synapse protection
27:33 Conclusions and clinical potential
30:12 Acknowledgements
Professor Markus Huber-Lang examines how activation of the complement system contributes to traumatic brain injury (TBI), from the immediate response to long-term neuroinflammation.
He presents evidence of complement activation within the brain and throughout the body following trauma, including its links with blood–brain barrier damage, coagulopathy and secondary brain injury. He also considers potential biomarkers and research suggesting that complement-targeted treatments could reduce neurological damage and improve recovery.
Markus Huber-Lang is Director of the Institute of Clinical and Experimental Trauma Immunology at University Hospital Ulm. His research focuses on the immune mechanisms underlying TBI and severe trauma. By combining experimental models with clinical studies, his team aims to identify therapeutic targets and biomarkers that could improve outcomes for people with severe brain injuries.
Presented at the Complement and the Brain Satellite Symposium during the 20th European Meeting on Complement in Human Disease on Tuesday 1 September 2026 in Cardiff. Find out more about the event at: https://emchd2026.org/
#TraumaticBrainInjury #Neuroinflammation #ComplementSystem
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Dementia Researcher works alongside events organisers to share their work. If you're organising a dementia research event and would like us to record or share your talks, to get them open access and to reach a wider audience, get in touch: https://www.dementiaresearcher.nihr.ac.uk
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Chapters
00:00 Introduction
00:32 TBI and the unmet clinical need
00:53 Primary and secondary brain injury
02:10 Evidence of complement activation after TBI
03:26 Patient evidence and blood–brain barrier damage
05:07 Local and systemic complement activation
06:42 Long-term complement activity after trauma
08:18 Biomarkers for TBI in polytrauma
10:29 Complement and coagulation crosstalk
12:18 Coagulopathy and thromboinflammation
13:53 Current treatments and their limitations
15:57 Complement-targeted damage control
18:03 Long-term effects of complement blockade
19:22 MBL, neutrophils and the blood–brain barrier
20:53 Translating complement therapies to patients
22:21 Conclusions and future priorities
23:58 Acknowledgements
Professor Paul Morgan examines evidence linking complement activation with neuroinflammation in Alzheimer’s disease and other neurodegenerative conditions.
He discusses genetic findings involving CR1, clusterin and other complement genes, alongside research into which brain cells produce complement and how dysregulation may contribute to synapse loss. He then explores the challenge of delivering treatments across the blood–brain barrier and presents brain-shuttle technology designed to transport complement-blocking antibodies into the brain.
In Alzheimer’s mouse models, a brain-penetrant antibody targeting C7 protected synapses, reduced microglial activation and neuronal degeneration, and improved cognition.
Paul Morgan is Professor of Immunology at Cardiff University and has studied the complement system for more than 30 years. His research has advanced understanding of CD59, the membrane attack complex and complement-triggered inflammasome activation. His current work focuses on complement in neurodegeneration and the development of new anti-complement treatments for dementia.
Presented at the Complement and the Brain Satellite Symposium during the 20th European Meeting on Complement in Human Disease on Tuesday 1 September 2026 in Cardiff. Find out more about the event at: https://emchd2026.org/
#Neurodegeneration #DementiaResearch #ComplementSystem
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Chapters
00:00 Introduction
00:50 Defining neurodegeneration
03:29 Neuroinflammation and complement
04:14 Alzheimer’s disease and treatment limitations
06:22 Genetic links between complement and Alzheimer’s
08:32 Investigating complement risk genes
09:51 CR1 in Alzheimer’s disease
14:00 Clusterin and synapses
16:07 Sources of complement in the brain
18:35 Early complement dysregulation
20:40 The complement therapeutics landscape
21:35 The blood–brain barrier challenge
24:05 Brain-shuttle technology
27:51 Developing brain-penetrant MAC blockers
28:29 Results in Alzheimer’s mouse models
30:43 Moving towards a human therapeutic
33:54 Conclusions and future directions
36:00 Acknowledgements
Dr Soyon Hong explains how neural activity regulates C1q deposition and microglial synapse elimination—and why this process can support brain homeostasis rather than simply cause damage.
She presents research showing that hyperactivation of a defined neural circuit causes region-specific C1q accumulation and the selective loss of less-active synapses. The talk also reveals roles for mature B cells, plasma cells and IgM, connecting immune activity at the brain’s borders with synaptic fate in ageing and neurodegenerative disease.
Dr Soyon Hong is a Group Leader at the UK Dementia Research Institute at University College London. Her laboratory studies neuro-glia-immune interactions at the synapse, including how microglia and astrocytes maintain synaptic homeostasis and how this communication breaks down in Alzheimer’s and Parkinson’s diseases. Her group also investigates immune signalling across brain borders and its influence on neuronal and synaptic fate.
Presented at the Complement and the Brain Satellite Symposium during the 20th European Meeting on Complement in Human Disease on Tuesday 1 September 2026 in Cardiff. Find out more about the event at: https://emchd2026.org/
#Neuroimmunology #ComplementSystem #SynapticPruning
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Dementia Researcher works alongside events organisers to share their work. If you're organising a dementia research event and would like us to record or share your talks, to get them open access and to reach a wider audience, get in touch: https://www.dementiaresearcher.nihr.ac.uk
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Chapters
00:00 Introduction
00:44 Brain immunity and synapse loss
02:16 Microglia, complement and synaptic pruning
04:51 What regulates synapse elimination?
06:32 Synaptic “eat-me” signals
10:11 Neural activity as a master regulator
12:13 Manipulating activity in the perforant pathway
15:09 C1q deposition and selective synapse loss
18:24 Reversing hyperactivity in an Alzheimer’s model
20:49 B cells and plasma cells at remodelling sites
25:57 IgM and C1q in synapse targeting
28:27 Homeostasis, ageing and neurodegeneration
ARIA in Alzheimer’s: complement and anti-amyloid antibody side effects — Cynthia Lemere
Professor Cynthia Lemere opens on ARIA, the amyloid-related imaging abnormalities that shadow anti-amyloid antibody therapy. Her preclinical work ties complement activation to vascular inflammation, blood–brain barrier leakage and microhaemorrhage — and an engineered antibody that prevented C1q binding cut microhaemorrhages by around 75%, which points at a route to safer treatment rather than simply a slower titration schedule.
Professor Lemere is Professor of Neurology at Harvard Medical School and the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital in Boston. Her laboratory investigates the role of immune proteins in Alzheimer’s, the clearance of amyloid-beta from the brain, and the development and progression of Alzheimer’s disease in people with Down syndrome.
C3aR in stroke recovery — Marcela Pekna
Professor Marcela Pekna turns to stroke, and to a finding that complicates any simple “block complement” strategy. C3a receptor signalling appears to do different jobs at different times: losing it may limit acute damage, but it also limits neuroplasticity later and worsens secondary neurodegeneration. Intranasal C3a given a week after stroke improved motor recovery, calmed astrocyte reactivity and supported synaptic plasticity and structural brain connectivity.
Marcela Pekna is Professor of Neuroimmunology at the University of Gothenburg, where she leads the Regenerative Neuroimmunology research group. Her work aims to develop treatments that promote recovery and regeneration following neurological injury and disease.
Complement after trauma in traumatic brain injury — Markus Huber-Lang
Professor Markus Huber-Lang covers traumatic brain injury, tracking complement activation both inside the brain and systemically, and its relationship with barrier damage, coagulopathy and secondary injury — along with what that might yield in biomarkers and complement-targeted treatment.
Markus Huber-Lang is Director of the Institute of Clinical and Experimental Trauma Immunology at University Hospital Ulm. Combining experimental models with clinical studies, his team aims to identify therapeutic targets and biomarkers that could improve outcomes for people with severe brain injuries.
Targeting complement in neurodegeneration — Paul Morgan
Professor Paul Morgan takes on the delivery problem head-on. Alongside the genetics implicating CR1, clusterin and other complement genes, and the question of which brain cells actually produce complement, he presents brain-shuttle technology built to carry complement-blocking antibodies across the blood–brain barrier. In Alzheimer’s mouse models, a brain-penetrant anti-C7 antibody protected synapses, reduced microglial activation and neuronal degeneration, and improved cognition.
Activity-dependent neuro-glia-immune regulation at the synapse — Soyon Hong
Dr Soyon Hong closes on the mechanism underneath much of the above: how neural activity itself governs C1q deposition and microglial synapse elimination, and why that process is normally homeostatic rather than destructive. Hyperactivating a defined circuit produces region-specific C1q accumulation and the selective loss of less-active synapses — and mature B cells, plasma cells and IgM turn out to have a hand in it, linking immune activity at the brain’s borders to synaptic fate in ageing and disease.
Dr Hong is a Group Leader at the UK Dementia Research Institute at University College London, where her laboratory studies neuro-glia-immune interactions at the synapse.
About the symposium
Taken together, the recordings make a reasonable case that complement is not one target but several, acting differently by disease, by cell type and by timepoint. That is harder to drug than a single switch, but it is a good deal more interesting — and it is a field where immunity and neurodegeneration research is moving quickly.
The Complement and the Brain satellite symposium ran in parallel with the Teaching Day on Tuesday 1 September 2026, as part of the 20th European Meeting on Complement in Human Disease, held in Cardiff from 1–5 September 2026. You can find out more about the meeting at emchd2026.org.
Professor Louise Serpell
Alzheimer's Association
