Dates: March 17-21, 2026
Location: Copenhagen, Denmark
Organizer: Kenes Group
Overview
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AD/PD 2026 showcased numerous emerging therapeutic targets beyond traditional amyloid, tau, and alpha-synuclein approaches. These novel targets represent new mechanistic insights and therapeutic opportunities for both Alzheimer's and Parkinson's diseases["@crews2023"].
APP Processing Modulators Beyond BACE and gamma-secretase, new approaches to modulate APP processing emerged:
... Dates: March 17-21, 2026
Location: Copenhagen, Denmark
Organizer: Kenes Group
Overview
Mermaid diagram (expand to render)
AD/PD 2026 showcased numerous emerging therapeutic targets beyond traditional amyloid, tau, and alpha-synuclein approaches. These novel targets represent new mechanistic insights and therapeutic opportunities for both Alzheimer's and Parkinson's diseases["@crews2023"].
APP Processing Modulators Beyond BACE and gamma-secretase, new approaches to modulate APP processing emerged:
Alpha-secretase activators — Promoting non-amyloidogenic processingAPP dimerization inhibitors — Targeting APP-APP interactionsADAM10 enhancers — Increasing alpha-secretase activity naturallyAmyloid Clearance Mechanisms
Microglial phagocytosis enhancers — Improving debris clearancePerivascular drainage facilitators — Supporting glymphatic functionAntibody engineering — Next-generation antibodies with enhanced brain penetrationTau-Targeted Approaches
Tau Acetylation Modulators The role of tau acetylation in disease progression represents a new target:
HDAC6 inhibitors — Reducing tau acetylation and aggregationp300 inhibitors — Preventing abnormal tau acetylationAcetyl-mimetic compounds — Blocking toxic acetylation sitesTau Oligomer Stabilizers Rather than preventing aggregation, some approaches stabilize non-toxic oligomers:
Oligomer-specific antibodies — Targeting toxic intermediatesAggregation inhibitors — Small molecules that block seedingTau post-translational modification modulators — Phosphatase and kinase modulatorsAlpha-Synuclein-Targeted Strategies
Aggregation Blockers
Small molecule inhibitors — Compounds preventing seed formationPeptide-based inhibitors — Designed peptides targeting aggregationNatural product derivatives — Repurposed compounds with anti-aggregation activityPropagation Inhibitors
Tunneling nanotube blockers — Preventing cell-to-cell spreadSynaptic transmission modulators — Reducing extracellular releaseMicroglial uptake enhancers — Improving clearance of extracellular speciesNeuroinflammation Targets
Microglial Modulation
TREM2 agonists — Enhancing beneficial microglial functionsCD33 inhibitors — Reducing inhibitory signalingCX3CR1 modulators — Fine-tuning microglial surveillanceComplement System Inhibition
C1q inhibitors — Preventing synaptic eliminationC3/C3aR antagonists — Blocking complement-mediated inflammationFactor D inhibitors — Upstream complement modulationPeripheral Immune Modulation
Gut-brain axis interventions — Microbiome-based therapiesPeripheral macrophage modulation — Reducing neuroinflammation spilloverBlood-brain barrier stabilizers — Preventing immune cell infiltration
Mitochondrial Quality Control
PINK1/Parkin activators — Enhancing mitophagyMFN1/2 modulators — Improving mitochondrial fusionmtDNA repair enhancers — Protecting mitochondrial genomeSirtuin activators — NAD+-boosting compoundsAMPK activators — Energy sensing pathway modulationKetone metabolism promoters — Alternative energy sourcesSynaptic Function Targets
Synaptic Plasticity Enhancers
mGluR modulators — Metabotropic glutamate receptor targetingNMDA receptor modulators — Optimizing glutamatergic signalingBDNF mimetics — Neurotrophic factor approachesSynapse Stabilization
PSD-95 stabilizers — Maintaining postsynaptic densitySynaptophysin modulators — Presynaptic vesicle proteinsRab GTPase modulators — Synaptic vesicle traffickingCellular Senescence Targets
Senolytic Approaches
Dasatinib/Quercetin combinations — Clearing senescent cellsFisetin — Natural senolytic compoundNavitoclax — Bcl-2 family inhibitorSenostatic Strategies
IL-8 inhibitors — Reducing senescence-associated inflammationp38 MAPK inhibitors — Blocking stress-induced senescencemTOR inhibitors — Rapamycin and analogsRNA-Targeted Approaches
ASO therapies — Antisense oligonucleotides targeting toxic RNARNAi approaches — siRNA-based gene silencingRNA splicing modulators — Correcting alternative splicingEpigenetic Therapies
DNA Methylation Modulators
DNMT inhibitors — DNA methyltransferase inhibitorsHDAC inhibitors — Histone deacetylase modulationBET inhibitors — Bromodomain inhibitionHistone Modifiers
H3K27me3 demethylases — Reversing repressive marksHAT activators — Promoting beneficial acetylationReader protein inhibitors — Blocking abnormal chromatin interactionsGene Therapy Approaches
Viral Vector Delivery
AAV serotypes — Optimized brain deliveryPromoter design — Cell-type specific expressionRegulatory elements — Controllable gene expressionNon-Viral Delivery
LNP formulations — Lipid nanoparticle deliveryExosome-based delivery — Natural vesicle therapeuticsDirect Brain Delivery — Convection-enhanced delivery methodsCombination Therapy Strategies
Rationale for Combinations
Multiple disease mechanisms require multi-target approaches
Synergistic effects can lower required doses
Addressing compensatory pathways prevents treatment escape
Emerging Combinations
Amyloid removal plus neuroinflammation modulation
Tau targeting plus synaptic protection
Alpha-synuclein plus mitochondrial enhancement
Clinical Trial Readiness
Biomarker Development
Target engagement biomarkers for each mechanism
Disease progression markers
Safety monitoring markers
Patient Stratification
Genetic subtyping
Biomarker-based selection
Phenotypic characterization
Future Directions
Precision medicine — Matching patients to specific targets based on biomarkersPrevention trials — Treating before symptoms appearPersonalized combinations — Tailored multi-target approachesContinuous monitoring — Adaptive trial designs with biomarker feedbackGlobal access — Ensuring equitable availability of new therapies
See Also
[AD/PD 2026 Conference](/events/adpd-2026)](/events)
[AD/PD 2026 Scientific Sessions](/events/adpd-2026)](/events)
[AD/PD 2026 Company Presentations](/events/adpd-2026)](/events)
[AD/PD 2026 Plenary Sessions](/events/adpd-2026-plenary-sessions)
References
[Crews L, et al., Molecular Neurodegeneration. 2023 (2023)](https://doi.org/10.1186/s13024-023-00626-3)
[Brundin P, et al., J Parkinsons Dis. 2024 (2024)](https://doi.org/10.3233/JPD-240001) Show full description