Dates: March 17-21, 2026
Location: Copenhagen, Denmark
Organizer: Kenes Group
Neuroinflammation was a major theme at AD/PD 2026, reflecting the growing recognition that inflammatory processes are not merely consequences but active drivers of neurodegeneration in both Alzheimer's and Parkinson's diseases. The conference featured extensive programming on microglial biology, complement system activation, and inflammatory signaling pathways.
Sessions explored the transition of microglia from protective to damaging states:
- DAM Pathway Activation: Mechanisms driving microglial activation and phenotypic changes in response to protein pathology
- Temporal Progression: How microglial states evolve across disease stages
- Sex Differences: Emerging data on gender-dependent microglial responses
TREM2 variants and their impact on microglial function were a key focus:
- TREM2 Signaling: Impact of risk variants on microglial response to amyloid and tau pathology
- Agonist Development: AL002 and AL003 clinical programs for TREM2 activation
- Biomarker Correlations: CSF and blood TREM2 as disease progression markers
- Therapeutic Window: Optimal timing for TREM2-targeted interventions
- Aging Effects: How aging primes microglia for exaggerated inflammatory responses
- Genetic Risk Factors: APOE4 and other genetic variants affecting microglial activation
- Environmental Modulators: Impact of lifestyle factors on microglial states
The NLRP3 inflammasome was highlighted as a key driver of neuroinflammation:
- Tau Pathology Connection: Role in tau phosphorylation and propagation
- IL-1β Signaling: Pro-inflammatory cytokine signaling in disease progression
- Gasdermin D: Pyroptosis and inflammatory cell death pathways
- Small Molecule Inhibitors: Latest developments in NLRP3-targeted therapies
- IL-1β: Role in synaptic dysfunction and cognitive decline
- IL-18: Contributions to neuroinflammation and neuronal death
- IL-1RA: Therapeutic potential of interleukin receptor antagonists
- C1q Involvement: Complement-mediated synaptic elimination in early disease
- C3 therapeutics: Novel complement inhibitors for neuroprotection
- Microglia-Neuron Crosstalk: Synaptic maintenance mechanisms
- C1q Inhibition: Anti-C1q antibodies for synaptic protection
- C3 Inhibition: Complement C3 as therapeutic target
- Timing Considerations: When to intervene in complement-mediated processes
- α-Synuclein-Induced Inflammation: How alpha-synuclein aggregates trigger microglial activation
- Chronic Activation: Progression from acute to chronic neuroinflammation
- Regional Patterns: Vulnerability of specific brain regions to inflammatory processes
- Gut-Brain Axis: Gastrointestinal inflammation and its contribution to PD
- Systemic Immunity: Peripheral immune cell infiltration into the CNS
- Blood-Brain Barrier: Disruption and inflammatory cell trafficking
- NSAID Trials: Lessons from past prevention trials
- Targeted Immunomodulation: More selective approaches than broad anti-inflammatory
- Microglia-Specific Targets: Novel targets unique to glial cells
- Timing of Intervention: Critical windows for inflammatory modulation
- Combination Approaches: Anti-inflammatory + disease-modifying combinations
- Biomarker-Driven Selection: Patient selection based on inflammatory markers
- YKL-40: Microglial activation marker
- IL-1β: Pro-inflammatory cytokine levels
- TREM2: Soluble TREM2 as disease marker
- TSPO PET: Translocator protein imaging for microglial activation
- MR Spectroscopy: Metabolic signatures of neuroinflammation
- TREM2 remains hot — Agonist and antagonist approaches both in clinical development
- Complement inhibition gaining traction — Multiple programs advancing to clinical trials
- Timing matters — Evidence for critical windows of intervention
- Cross-disease mechanisms — Common inflammatory pathways between AD and PD
- Biomarker integration — Neuroinflammation biomarkers entering clinical trials