AD/PD 2026 Neuroinflammation

Dates: March 17-21, 2026 Location: Copenhagen, Denmark Organizer: Kenes Group

Overview

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^{1Neuroinflammation in Alzheimer's disease. Lancet Neurol. 20242024 · DOI 10.1016/S1474-4422(24)00123-6Open reference}. The conference featured extensive programming on microglial biology, complement system activation, and inflammatory signaling pathways.

Microglial Biology

Disease-Associated Microglia (DAM)

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 Biology

TREM2 variants and their impact on microglial function were a key focus^{2TREM2 and neurodegenerative diseases. Nat Rev Neurol. 20232023 · DOI 10.1038/s41582-023-00800-1Open reference}:

• 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

Microglial Priming

• 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

Inflammasome Activation

NLRP3 Inflammasome

The NLRP3 inflammasome was highlighted as a key driver of neuroinflammation^{3NLRP3 inflammasome in neurodegeneration. Nat Rev Neurosci. 20222022 · DOI 10.1038/s41583-022-00587-4Open reference}:

• 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-1 Family Cytokines

• 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

Complement System

Synaptic Pruning

• C1q Involvement: Complement-mediated synaptic elimination in early disease

• C3 therapeutics: Novel complement inhibitors for neuroprotection

• Microglia-Neuron Crosstalk: Synaptic maintenance mechanisms

Therapeutic Approaches

• C1q Inhibition: Anti-C1q antibodies for synaptic protection

• C3 Inhibition: Complement C3 as therapeutic target

• Timing Considerations: When to intervene in complement-mediated processes

Parkinson’s Disease-Specific Inflammation

Microglial Activation in PD

• 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

Peripheral-Brain Cross-Talk

• 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

Therapeutic Strategies

Anti-Inflammatory Approaches

• 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

Disease Modification vs Symptomatic Relief

• Timing of Intervention: Critical windows for inflammatory modulation

• Combination Approaches: Anti-inflammatory + disease-modifying combinations

• Biomarker-Driven Selection: Patient selection based on inflammatory markers

Biomarkers of Neuroinflammation

Fluid Biomarkers

• YKL-40: Microglial activation marker

• IL-1β: Pro-inflammatory cytokine levels

• TREM2: Soluble TREM2 as disease marker

Imaging Biomarkers

• TSPO PET: Translocator protein imaging for microglial activation

• MR Spectroscopy: Metabolic signatures of neuroinflammation

Key Takeaways

1. TREM2 remains hot — Agonist and antagonist approaches both in clinical development

2. Complement inhibition gaining traction — Multiple programs advancing to clinical trials

3. Timing matters — Evidence for critical windows of intervention

4. Cross-disease mechanisms — Common inflammatory pathways between AD and PD

5. Biomarker integration — Neuroinflammation biomarkers entering clinical trials

See Also

• AD/PD 2026 Conference](/events)

• AD/PD 2026 Scientific Sessions](/events)

• AD/PD 2026 Emerging Therapeutic Targets](/events)

• AD/PD 2026 Clinical Trial Updates](/events)

• Events Index