Top 50 hypotheses ranked by tournament Elo, market confidence, debate depth, and citation provenance
| # | Hypothesis | Elo | Market | Debates | Citations | Updated | Score |
|---|---|---|---|---|---|---|---|
| 🥇 |
TREM2-Dependent Microglial Senescence Transition
mechanistic
• TREM2
• neurodegeneration
|
208871 matches | 0.541 Market | 5 Transcript | 72 | 2026-04-26 | 0.618 |
| 🥈 |
SASP-Mediated Complement Cascade Amplification
mechanistic
• C1Q/C3
• neurodegeneration
|
208071 matches | 0.910 Market | 3 Transcript | 66 | 2026-04-28 | 0.822 |
| 🥉 |
TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegeneration
mechanistic
• TREM2
• neurodegeneration
|
207334 matches | 0.990 Market hub | 5 Transcript | 54 | 2026-04-27 | 0.716 |
| 4 |
eIF2α Phosphorylation Imbalance Creates Integrated Stress Response Overf
mechanistic
• EIF2S1,eIF2α,PERK,GCN2,ATF4,ATF5,CHOP,DDIT3,integrated stress response,protein synthesis
• als
|
19854 matches | 0.693 Market hub | 1 No transcript | 15 | 2026-04-27 | 0.896 |
| 5 |
Nutrient-Sensing Epigenetic Circuit Reactivation
mechanistic
• SIRT1
• neurodegeneration
|
198470 matches | 0.907 Market | 4 Transcript | 90 | 2026-04-28 | 0.700 |
| 6 |
IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microglia Interface
mechanistic
• IL6R, IL6
• neuroinflammation
|
189610 matches | 0.806 Market | 1 Transcript | 29 | 2026-04-26 | 0.831 |
| 7 |
Prime Editing Precision Correction of APOE4 to APOE3 in Microglia
mechanistic
• APOE
• neurodegeneration
|
187739 matches | 0.612 Market hub | 3 Transcript | 38 | 2026-04-11 | 0.850 |
| 8 |
Transcriptional Autophagy-Lysosome Coupling
mechanistic
• FOXO1
• neurodegeneration
|
182659 matches | 0.882 Market | 2 Transcript | 97 | 2026-04-28 | 0.777 |
| 9 |
STMN2 Cryptic Exon Inclusion is the Earliest Loss-of-Function Marker of
mechanistic
• TARDBP
• als
|
18104 matches | 0.596 Market hub | 1 Transcript | 5 | 2026-04-28 | 0.760 |
| 10 |
Chromatin Remodeling-Mediated Nutrient Sensing Restoration
mechanistic
• SMARCA4
• neurodegeneration
|
17922 matches | 0.637 Market hub | 4 Transcript | 43 | 2026-04-27 | 0.764 |
| 11 |
Aryl Hydrocarbon Receptor (AHR) Activation in B Cells Determines AQP4 To
mechanistic
• AHR, IL10, TNFRSF13B, TIGIT, FOXP3
• neuroinflammation
|
179110 matches | 0.546 Market hub | 2 Transcript | 12 | 2026-04-13 | 0.738 |
| 12 |
hnRNP A2/B1 Staufen2-Mediated Axonal RNA Granule Transport Failure Drive
mechanistic
• HNRNPA2B1,STAU2,PRMT1,GSK3B,MAP1B,β-actin,axonal transport machinery
• als
|
17744 matches | 0.731 Market hub | 1 No transcript | 9 | 2026-04-27 | 0.851 |
| 13 |
Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in Neurodege
mechanistic
• NLRP3, CASP1, IL1B, PYCARD
• neurodegeneration
|
176766 matches | 0.675 Market hub | 1 Transcript | 51 | 2026-04-13 | 0.924 |
| 14 |
PDE4 Inhibition as Inflammatory Reset for PD Oligodendrocytes
mechanistic
• PDE4A, PDE4B, PDE4D
• neuroinflammation
|
174110 matches | 0.606 Market hub | 1 Transcript | 13 | 2026-04-13 | 0.779 |
| 15 |
SFPQ Paralog Displacement Triggers Cryptic Polyadenylation and Global RN
mechanistic
• SFPQ,NONO,PSP1,TARDBP,poly(A) machinery,CPSF,PABPN1
• als
|
17264 matches | 0.731 Market hub | 1 No transcript | 5 | 2026-04-27 | 0.864 |
| 16 |
ACSL4-Driven Ferroptotic Priming in Disease-Associated Microglia
mechanistic
• ACSL4
• alzheimers
|
171210 matches | 0.847 Market | 9 Transcript | 91 | 2026-04-28 | 0.891 |
| 17 |
Vascular mural cell degeneration precedes and exacerbates parenchymal pa
mechanistic
• PDGFRB
• alzheimers
|
169643 matches | 0.552 Market hub | 4 Transcript | 18 | 2026-04-27 | 0.661 |
| 18 |
APOE ε4 Drives Lipid Droplet Accumulation in a Unique Lipid-Associated M
mechanistic
• APOE
• alzheimer
|
16914 matches | 0.591 Market hub | 2 Transcript | 5 | 2026-04-28 | 0.697 |
| 19 |
RBM45 Liquid-Liquid Phase Separation Dominance Hijacks RNA Processing Co
mechanistic
• RBM45,GSK3B,TDP-43,TARDBP,hnRNP A1,HNRNPA1,phase separation,Liquid droplet
• als
|
16614 matches | 0.731 Market hub | 1 No transcript | 7 | 2026-04-27 | 0.868 |
| 20 |
Astrocyte-specific autophagy deficiency induces NADPH oxidase-mediated o
mechanistic
• ATG7
• als
|
16564 matches | 0.490 Market hub | 1 Transcript | 5 | 2026-04-27 | 0.390 |
| 21 |
ubiquitylation-dependent turnover is the actionable driver in: How do AL
mechanistic
• ubiquitylation-dependent turnover
• neurodegeneration
|
160719 matches | 0.519 Market hub | 3 Transcript | 10 | 2026-04-26 | 0.344 |
| 22 |
TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegeneration
mechanistic
• TREM2
• neurodegeneration
|
15792 matches | 0.633 Market hub | 3 Transcript | 54 | 2026-04-26 | 0.708 |
| 23 |
tight-junction remodeling is the actionable driver in: Blood-brain barri
mechanistic
• tight-junction remodeling
• neurodegeneration
|
157419 matches | 0.600 Market hub | 3 Transcript | 10 | 2026-04-26 | 0.362 |
| 24 |
TREM2-ASM Crosstalk in Microglial Lysosomal Senescence
mechanistic
• SMPD1
• neurodegeneration
|
15602 matches | 0.609 Market hub | 3 Transcript | 54 | 2026-04-26 | 0.713 |
| 25 |
X-Linked KDM6A Escapes X-Inactivation to Drive Female-Biased Microglial
mechanistic
• KDM6A
• alzheimer
|
15604 matches | 0.582 Market hub | 1 Transcript | 5 | 2026-04-28 | 0.675 |
| 26 |
age-linked CpG drift is the actionable driver in: Are DNA methylation ch
mechanistic
• age-linked CpG drift
• neurodegeneration
|
155819 matches | 0.587 Market hub | 3 Transcript | 10 | 2026-04-26 | 0.344 |
| 27 |
Arginine Methylation Loss on FUS RGG Domains Drives Irreversible Phase T
mechanistic
• FUS
• als
|
15504 matches | 0.581 Market hub | 1 Transcript | 5 | 2026-04-28 | 0.680 |
| 28 |
age-linked CpG drift is the actionable driver in: Are age-related DNA me
mechanistic
• age-linked CpG drift
• neurodegeneration
|
154719 matches | 0.587 Market hub | 3 Transcript | 10 | 2026-04-26 | 0.344 |
| 29 |
Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopat
mechanistic
• AIM2, CASP1, IL1B, PYCARD, TARDBP
• neurodegeneration
|
154610 matches | 0.653 Market hub | 1 Transcript | 31 | 2026-04-26 | 0.824 |
| 30 |
TLR4 priming is the actionable driver in: How does gut microbiome dysbio
mechanistic
• TLR4 priming
• neurodegeneration
|
154019 matches | 0.539 Market hub | 3 Transcript | 10 | 2026-04-26 | 0.343 |
| 31 |
Microglial-Mediated Tau Clearance Dysfunction via TREM2 Receptor Impairm
mechanistic
• MAPT
• neuroscience
|
153612 matches | 0.551 Market hub | 18 Transcript | 17 | 2026-04-27 | 0.937 |
| 32 |
ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes
mechanistic
• ACSL4
• alzheimers
|
15332 matches | 0.580 Market hub | 8 Transcript | 44 | 2026-04-28 | 0.779 |
| 33 |
Digital Twin-Guided Metabolic Reprogramming
mechanistic
• PPARGC1A/PRKAA1
• neurodegeneration
|
152024 matches | 0.624 Market | 2 Transcript | 53 | 2026-04-28 | 0.550 |
| 34 |
Layer V excitatory neurons show selectively enhanced vulnerability throu
mechanistic
• SLC17A7
• alzheimers
|
151635 matches | 0.573 Market hub | 4 Transcript | 2 | 2026-04-27 | 0.632 |
| 35 |
TIA1 Low-Complexity Domain Oxidation Drives Aberrant Stress Granule Asse
mechanistic
• TIA1,TDP-43,TARDBP,G3BP1,MAPK1,Oxidative stress response
• als
|
15154 matches | 0.699 Market hub | 1 No transcript | 4 | 2026-04-27 | 0.810 |
| 36 |
plasma LPS-binding protein separates causal from compensatory states in:
mechanistic
• plasma LPS-binding protein
• neurodegeneration
|
150919 matches | 0.554 Market hub | 3 Transcript | 6 | 2026-04-26 | 0.346 |
| 37 |
TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegeneration
mechanistic
• TREM2
• neurodegeneration
|
15076 matches | 0.580 Market hub | 3 Transcript | 21 | 2026-04-11 | 0.892 |
| 38 |
plasma GFAP separates causal from compensatory states in: Blood-brain ba
mechanistic
• plasma GFAP
• neurodegeneration
|
150519 matches | 0.554 Market hub | 3 Transcript | 10 | 2026-04-26 | 0.346 |
| 39 |
K48/K63 ubiquitin chain balance separates causal from compensatory state
mechanistic
• K48/K63 ubiquitin chain balance
• neurodegeneration
|
150119 matches | 0.556 Market hub | 3 Transcript | 10 | 2026-04-26 | 0.335 |
| 40 |
Complement C1QA Spatial Gradient in Cortical Layers
mechanistic
• C1QA
• alzheimers
|
15000 matches | 0.650 Market | 3 Transcript | 20 | 2026-04-27 | 0.678 |
| 41 |
APOE-TREM2 Ligand Availability Dysfunction in Neurodegeneration
mechanistic
• APOE
• neurodegeneration
|
15000 matches | 0.649 Market | 3 Transcript | 35 | 2026-04-26 | 0.649 |
| 42 |
TREM2-Mediated Mitochondrial Dysfunction in Neurodegeneration
mechanistic
• TREM2
• neurodegeneration
|
15000 matches | 0.645 Market | 3 Transcript | 35 | 2026-04-26 | 0.642 |
| 43 |
TREM2-Driven Senescence Biomarker Index for Predicting Neurodegeneration
mechanistic
• TREM2
• neurodegeneration
|
15000 matches | 0.642 Market | 3 Transcript | 35 | 2026-04-26 | 0.642 |
| 44 |
VCP-Mediated Autophagy Enhancement
mechanistic
• VCP
• alzheimers
|
15000 matches | 0.640 Market hub | 2 Transcript | 36 | 2026-04-12 | 0.595 |
| 45 |
Excitatory Neuron Vulnerability via SLC17A7 Downregulation
mechanistic
• SLC17A7
• alzheimers
|
15000 matches | 0.570 Market | 3 Transcript | 14 | 2026-04-26 | 0.675 |
| 46 |
GluN2B-Mediated Thalamocortical Control of Glymphatic Tau Clearance
mechanistic
• GRIN2B
• neuroscience
|
15000 matches | 0.569 Market hub | 18 Transcript | 30 | 2026-04-27 | 0.964 |
| 47 |
TREM2-Mediated Oligodendrocyte-Microglia Signaling in White Matter Neuro
mechanistic
• TREM2
• neurodegeneration
|
15000 matches | 0.556 Market hub | 3 Transcript | 54 | 2026-04-21 | 0.587 |
| 48 |
TREM2-Astrocyte Communication in Microglial Dysfunction
mechanistic
• TREM2
• neurodegeneration
|
15000 matches | 0.556 Market hub | 3 Transcript | 35 | 2026-04-21 | 0.579 |
| 49 |
TREM2-Mediated Oligodendrocyte-Microglia Metabolic Coupling in White Mat
mechanistic
• TREM2
• neurodegeneration
|
15000 matches | 0.554 Market hub | 3 Transcript | 54 | 2026-04-17 | 0.649 |
| 50 |
Age-Dependent TREM2 Signaling Disrupts Astrocyte-Microglia Communication
mechanistic
• TREM2
• neurodegeneration
|
15000 matches | 0.554 Market hub | 3 Transcript | 54 | 2026-04-17 | 0.649 |