Dates: March 17-21, 2026
Location: Copenhagen, Denmark
Organizer: Kenes Group
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.
Beyond BACE and gamma-secretase, new approaches to modulate APP processing emerged:
- Alpha-secretase activators — Promoting non-amyloidogenic processing
- APP dimerization inhibitors — Targeting APP-APP interactions
- ADAM10 enhancers — Increasing alpha-secretase activity naturally
- Microglial phagocytosis enhancers — Improving debris clearance
- Perivascular drainage facilitators — Supporting glymphatic function
- Antibody engineering — Next-generation antibodies with enhanced brain penetration
The role of tau acetylation in disease progression represents a new target:
- HDAC6 inhibitors — Reducing tau acetylation and aggregation
- p300 inhibitors — Preventing abnormal tau acetylation
- Acetyl-mimetic compounds — Blocking toxic acetylation sites
Rather than preventing aggregation, some approaches stabilize non-toxic oligomers:
- Oligomer-specific antibodies — Targeting toxic intermediates
- Aggregation inhibitors — Small molecules that block seeding
- Tau post-translational modification modulators — Phosphatase and kinase modulators
- Small molecule inhibitors — Compounds preventing seed formation
- Peptide-based inhibitors — Designed peptides targeting aggregation
- Natural product derivatives — Repurposed compounds with anti-aggregation activity
- Tunneling nanotube blockers — Preventing cell-to-cell spread
- Synaptic transmission modulators — Reducing extracellular release
- Microglial uptake enhancers — Improving clearance of extracellular species
- TREM2 agonists — Enhancing beneficial microglial functions
- CD33 inhibitors — Reducing inhibitory signaling
- CX3CR1 modulators — Fine-tuning microglial surveillance
- C1q inhibitors — Preventing synaptic elimination
- C3/C3aR antagonists — Blocking complement-mediated inflammation
- Factor D inhibitors — Upstream complement modulation
- PINK1/Parkin activators — Enhancing mitophagy
- MFN1/2 modulators — Improving mitochondrial fusion
- mtDNA repair enhancers — Protecting mitochondrial genome
- Sirtuin activators — NAD+-boosting compounds
- AMPK activators — Energy sensing pathway modulation
- Ketone metabolism promoters — Alternative energy sources
- mGluR modulators — Metabotropic glutamate receptor targeting
- NMDA receptor modulators — Optimizing glutamatergic signaling
- BDNF mimetics — Neurotrophic factor approaches
- PSD-95 stabilizers — Maintaining postsynaptic density
- Synaptophysin modulators — Presynaptic vesicle proteins
- Rab GTPase modulators — Synaptic vesicle trafficking
- Dasatinib/Quercetin combinations — Clearing senescent cells
- Fisetin — Natural senolytic compound
- Navitoclax — Bcl-2 family inhibitor
- IL-8 inhibitors — Reducing senescence-associated inflammation
- p38 MAPK inhibitors — Blocking stress-induced senescence
- mTOR inhibitors — Rapamycin and analogs
- ASO therapies — Antisense oligonucleotides targeting toxic RNA
- RNAi approaches — siRNA-based gene silencing
- RNA splicing modulators — Correcting alternative splicing
- DNMT inhibitors — DNA methyltransferase inhibitors
- HDAC inhibitors — Histone deacetylase modulation
- BET inhibitors — Bromodomain inhibition
- H3K27me3 demethylases — Reversing repressive marks
- HAT activators — Promoting beneficial acetylation
- Reader protein inhibitors — Blocking abnormal chromatin interactions
- AAV serotypes — Optimized brain delivery
- Promoter design — Cell-type specific expression
- Regulatory elements — Controllable gene expression
- LNP formulations — Lipid nanoparticle delivery
- Exosome-based delivery — Natural vesicle therapeutics
- Direct Brain Delivery — Convection-enhanced delivery methods
- Multiple disease mechanisms require multi-target approaches
- Synergistic effects can lower required doses
- Addressing compensatory pathways prevents treatment escape
- Amyloid removal plus neuroinflammation modulation
- Tau targeting plus synaptic protection
- Alpha-synuclein plus mitochondrial enhancement
- Target engagement biomarkers for each mechanism
- Disease progression markers
- Safety monitoring markers
- Genetic subtyping
- Biomarker-based selection
- Phenotypic characterization
- Precision medicine — Matching patients to specific targets based on biomarkers
- Prevention trials — Treating before symptoms appear
- Personalized combinations — Tailored multi-target approaches
- Continuous monitoring — Adaptive trial designs with biomarker feedback
- Global access — Ensuring equitable availability of new therapies