SciDEX — Hypothesis Leaderboard

#	Hypothesis	Score	Dimensions	Market	Debates
🥇	Closed-loop transcranial focused ultrasound with 40Hz gamma entrainment therapeutic • PVALB • Alzheimer's disease	1.000	Nov 0.78 Feas 0.86 Imp 0.80 Drug 0.75	0.964	2
🥈	Metabolic Reprogramming to Reverse Senescence therapeutic • SIRT1,PGC1A,NAMPT • —	1.000	Nov 0.60 Feas 0.90 Imp 0.82 Drug 0.90	0.980	2
🥉	TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegeneration mechanistic • TREM2 • neurodegeneration	0.990	Nov 0.72 Feas 0.82 Imp 0.78 Drug 0.65	0.870	3
4	SASP Modulation Rather Than Cell Elimination therapeutic • NFKB1,IL1B,BDNF • —	0.981	Nov 0.70 Feas 0.80 Imp 0.78 Drug 0.80	0.968	1
5	TREM2-Dependent Microglial Senescence Transition mechanistic • TREM2 • neurodegeneration	0.950	Nov 0.78 Feas 0.72 Imp 0.91 Drug 0.65	0.968	3
6	Closed-loop transcranial focused ultrasound targeting EC-II SST interneu therapeutic • SST • Alzheimer's disease	0.948	Nov 0.00 Feas 0.00 Imp 0.00 Drug 0.75	0.961	2
7	Closed-loop optogenetic targeting PV interneurons to restore theta-gamma therapeutic • PVALB • Alzheimer's disease	0.944	Nov 0.00 Feas 0.00 Imp 0.00 Drug 0.75	0.824	2
8	PLCG2 Allosteric Modulation as a Precision Therapeutic for TREM2-Depende — • PLCG2 • neurodegeneration	0.941	Nov 0.85 Feas 0.42 Imp 0.72 Drug 0.35	0.821	1
9	Plasma p-tau217-Triggered Exosome Dosing Maximizes lncRNA-0021 Therapeut — • CSF p-tau217 (biomarker), lncRNA-0021, hUC-MSC exosomes • molecular neurobiology	0.938	Nov 0.50 Feas 0.85 Imp 0.65 Drug 0.80	0.867	1
10	Multi-Biomarker Composite Index Surpassing Amyloid PET for Treatment Res — • COMPOSITE_BIOMARKER • neurodegeneration	0.933	Nov 0.65 Feas 0.92 Imp 0.88 Drug 0.95	0.865	1
11	Closed-loop focused ultrasound targeting CA1 PV interneurons to restore therapeutic • PVALB • Alzheimer's disease	0.927	Nov 0.88 Feas 0.65 Imp 0.78 Drug 0.45	0.849	3
12	Closed-loop transcranial focused ultrasound targeting EC-II SST interneu therapeutic • SST • Alzheimer's disease	0.922	Nov 0.90 Feas 0.45 Imp 0.80 Drug 0.75	0.852	3
13	CYP46A1 Gene Therapy for Age-Related TREM2-Mediated Microglial Senescenc therapeutic • CYP46A1 • neurodegeneration	0.921	Nov 0.75 Feas 0.60 Imp 0.80 Drug 0.55	0.801	1
14	Autophagy-Senescence Axis Therapeutic Window therapeutic • ATG7,BCL2,BCL2L1 • —	0.921	Nov 0.80 Feas 0.60 Imp 0.00 Drug 0.70	0.928	1
15	Selective Acid Sphingomyelinase Modulation Therapy therapeutic • SMPD1 • neurodegeneration	0.920	Nov 0.70 Feas 0.90 Imp 0.85 Drug 0.95	0.800	1
16	HK2-Dependent Metabolic Checkpoint as the Gatekeeper of DAM Transition — • HK2 • neurodegeneration	0.919	Nov 0.80 Feas 0.55 Imp 0.75 Drug 0.60	0.907	1
17	Palmitoylethanolamide-Based Endocannabinoid Therapy therapeutic • PPARA • —	0.919	Nov 0.00 Feas 0.00 Imp 0.00 Drug 0.90	0.799	2
18	CYP46A1 Overexpression Gene Therapy therapeutic • CYP46A1 • neurodegeneration	0.919	Nov 0.95 Feas 0.60 Imp 0.90 Drug 0.65	0.925	1
19	Chromatin Remodeling-Mediated Nutrient Sensing Restoration mechanistic • SMARCA4 • neurodegeneration	0.914	Nov 0.72 Feas 0.92 Imp 0.82 Drug 0.90	0.924	3
20	Closed-loop transcranial focused ultrasound to restore hippocampal gamma therapeutic • CCK • Alzheimer's disease	0.912	Nov 0.00 Feas 0.00 Imp 0.00 Drug 0.75	0.874	2
21	SASP-Mediated Complement Cascade Amplification mechanistic • C1Q/C3 • neurodegeneration	0.910	Nov 0.85 Feas 0.75 Imp 0.80 Drug 0.85	0.931	2
22	TREM2-ASM Crosstalk in Microglial Lysosomal Senescence mechanistic • SMPD1 • neurodegeneration	0.910	Nov 0.70 Feas 0.80 Imp 0.76 Drug 0.65	0.790	3
23	TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegeneration mechanistic • TREM2 • neurodegeneration	0.907	Nov 0.72 Feas 0.82 Imp 0.78 Drug 0.65	0.813	3
24	Nutrient-Sensing Epigenetic Circuit Reactivation mechanistic • SIRT1 • neurodegeneration	0.907	Nov 0.70 Feas 0.95 Imp 0.85 Drug 0.90	0.835	3
25	Closed-loop focused ultrasound targeting EC-II SST interneurons to resto therapeutic • SST • Alzheimer's disease	0.900	Nov 0.79 Feas 0.87 Imp 0.81 Drug 0.75	0.952	2
26	CSF1R Inhibition-Mediated Microglial Replacement as a State Transition R — • CSF1R • neurodegeneration	0.898	Nov 0.70 Feas 0.55 Imp 0.75 Drug 0.80	0.846	1
27	Closed-loop tACS targeting EC-II SST interneurons to block tau propagati therapeutic • SST • Alzheimer's disease	0.896	Nov 0.78 Feas 0.86 Imp 0.82 Drug 0.75	0.776	2
28	SIRT1-Mediated Reversal of TREM2-Dependent Microglial Senescence mechanistic • SIRT1 • neurodegeneration	0.895	Nov 0.70 Feas 0.80 Imp 0.76 Drug 0.65	0.831	3
29	TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegeneration mechanistic • TREM2 • neurodegeneration	0.892	Nov 0.72 Feas 0.68 Imp 0.82 Drug 0.45	0.772	3
30	Hypothesis 4: Metabolic Coupling via Lactate-Shuttling Collapse — • SLC16A1, SLC16A7, LDHA, PDHA1 • neurodegeneration	0.892	Nov 0.62 Feas 0.70 Imp 0.68 Drug 0.75	0.840	1
31	Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in Neurodege mechanistic • NLRP3, CASP1, IL1B, PYCARD • neurodegeneration	0.888	Nov 0.00 Feas 0.00 Imp 0.00 Drug 0.90	0.914	1
32	Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Partially Irre combination • APP/PSEN1 (Aβ production), CHAT (cholinergic synthesis) • —	0.887	Nov 0.55 Feas 0.60 Imp 0.85 Drug 0.00	0.815	1
33	H1: TREM2 Agonism to Redirect APOE4-Enhanced Microglia from Synapse Prun therapeutic • TREM2 • neurodegeneration	0.887	Nov 0.65 Feas 0.82 Imp 0.75 Drug 0.80	0.897	1
34	Focused Ultrasound with Microbubble Contrast Agents for Antibody CNS Del — • CLDN5/ZO-1 tight junction complex; KDR/VEGFR2 • neurodegeneration	0.886	Nov 0.75 Feas 0.88 Imp 0.90 Drug 0.85	0.892	1
35	TREM2-APOE Axis Dissociation for Selective DAM Activation — • TREM2-APOE axis • neurodegeneration	0.886	Nov 0.78 Feas 0.35 Imp 0.68 Drug 0.28	0.865	1
36	Epigenetic Priming Ketone Protocol — • HDAC2/HDAC3 • metabolic neuroscience	0.882	Nov 0.90 Feas 0.80 Imp 0.70 Drug 0.90	0.834	1
37	Transcriptional Autophagy-Lysosome Coupling mechanistic • FOXO1 • neurodegeneration	0.882	Nov 0.80 Feas 0.75 Imp 0.78 Drug 0.70	0.900	2
38	TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegeneration mechanistic • TREM2 • neurodegeneration	0.880	Nov 0.75 Feas 0.68 Imp 0.82 Drug 0.45	0.921	4
39	Optimized Temporal Window for Metabolic Boosting Therapy Determines Succ — • IFNG • neurodegeneration	0.879	Nov 0.75 Feas 0.50 Imp 0.75 Drug 0.60	0.872	1
40	TREM2-Mediated Astrocyte-Microglia Cross-Talk in Neurodegeneration mechanistic • TREM2 • neurodegeneration	0.875	Nov 0.75 Feas 0.68 Imp 0.82 Drug 0.45	0.918	3
41	GluN2B-Mediated Thalamocortical Control of Glymphatic Tau Clearance mechanistic • GRIN2B • neuroscience	0.869	Nov 0.00 Feas 0.00 Imp 0.00 Drug 0.95	0.749	3
42	TREM2-Mediated Cholesterol Dysregulation in Microglial Senescence mechanistic • CYP46A1 • neurodegeneration	0.869	Nov 0.78 Feas 0.65 Imp 0.75 Drug 0.58	0.891	3
43	Complement Cascade Inhibition Synaptic Protection — • — • neurodegeneration	0.867	Nov 0.70 Feas 0.55 Imp 0.72 Drug 0.65	0.808	1
44	Closed-loop tACS targeting EC-II PV interneurons to enhance perisomatic therapeutic • PVALB • Alzheimer's disease	0.867	Nov 0.78 Feas 0.65 Imp 0.75 Drug 0.45	0.811	2
45	Closed-loop focused ultrasound targeting EC-II PV interneurons to restor therapeutic • PVALB • Alzheimer's disease	0.863	Nov 0.85 Feas 0.45 Imp 0.75 Drug 0.30	0.885	3
46	Optogenetic restoration of hippocampal gamma oscillations via selective therapeutic • PVALB • Alzheimer's disease	0.863	Nov 0.78 Feas 0.45 Imp 0.68 Drug 0.35	0.811	3
47	Hippocampal CA3-CA1 synaptic rescue via DHHC2-mediated PSD95 palmitoylat therapeutic • BDNF • Alzheimer's disease	0.861	Nov 0.82 Feas 0.70 Imp 0.83 Drug 0.68	0.811	3
48	Closed-loop transcranial focused ultrasound to restore hippocampal gamma therapeutic • PVALB • Alzheimer's disease	0.858	Nov 0.80 Feas 0.88 Imp 0.82 Drug 0.75	0.981	2
49	TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger f — • NAMPT • neurodegeneration	0.858	Nov 0.65 Feas 0.50 Imp 0.75 Drug 0.60	0.738	1
50	Closed-loop tACS targeting EC-II PV interneurons to suppress burst firin therapeutic • PVALB • Alzheimer's disease	0.857	Nov 0.78 Feas 0.87 Imp 0.81 Drug 0.75	0.918	2

🏆 Hypothesis Leaderboard

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