ASM

Extended debate: CYP46A1 Overexpression Gene Therapy

closed · Rounds: 6 · Score: 0.95 · 2026-04-27

Hypothesis debate: Membrane Cholesterol Gradient Modulators

closed · Rounds: 4 · Score: 0.50 · 2026-04-27

Hypothesis debate: Selective Acid Sphingomyelinase Modulation Therapy

closed · Rounds: 4 · Score: 0.40 · 2026-04-27

Hypothesis debate: CYP46A1 Overexpression Gene Therapy

closed · Rounds: 4 · Score: 0.40 · 2026-04-27

Investigate how lipid raft composition (cholesterol metabolism, sphingolipids) c

closed · Rounds: 5 · Score: 0.93 · 2026-04-11

CSF/Plasma AQP4 Polarization Index as a Novel Biomarker of Astrocyte Glymphatic

Score: 0.705 · unknown disease · 2026-04-26

Aquaporin-4 (AQP4) water channels are normally concentrated at astrocyte end-feet ensheathing cerebral microvessels. Ear

Plasma Claudin-5 Proteolytic Fragments Distinguish Paracellular BBB Breakdown fr

Score: 0.705 · unknown disease · 2026-04-26

Claudin-5 is the most abundant tight junction protein in brain endothelial cells and is specifically degraded during ear

Plasma D-Dimer Elevation Reflects Fibrinogen Leakage and Secondary Fibrinolysis

Score: 0.685 · unknown disease · 2026-04-26

Plasma fibrinogen leaks across the compromised BBB and undergoes coagulation cascade activation and cross-linking by fac

RNA-binding protein condensate maturation from reversible phase separation to am

Score: 0.626 · neurodegeneration · 2026-04-28

RNA-binding protein condensate maturation from reversible phase separation to amyloid-like aggregation should produce a

Cell-state stratification is required to resolve Causal Sequence of TDP-43 Nucle

Score: 0.612 · neurodegeneration · 2026-04-28

The question is likely underpowered or misleading unless analyses preserve the key strata: TDP-43, ALS. Averaging across

Perturbation-first validation should precede therapeutic claims for Causal Seque

Score: 0.608 · neurodegeneration · 2026-04-28

The debate supports treating this as a validation program before ranking it as a therapy. Perturbation should move a pro

Neurovascular Permeability Score (NVPS): Composite Plasma + Imaging Biomarker Pa

Score: 0.600 · unknown disease · 2026-04-26

A LASSO-optimized composite score integrating plasma GFAP, S100B, NFL, soluble PDGFR-β, and claudin-5 fragments to achie

C9orf72 Nucleocytoplasmic Transport Rescue for ALS/FTD

Score: 0.597 · neurodegeneration · 2026-05-06

C9orf72 intronic GGGGCC repeats produce dipeptide repeat proteins and RNA foci that sequester nuclear import factors (TN

RNA Metabolism and Nucleocytoplasmic Transport Defects

Score: 0.580 · neurodegeneration · 2026-04-28

Impaired RNA processing and disrupted nucleocytoplasmic transport represent a convergent molecular phenotype, but most c

Complement C1q Suppression as Mechanism Linking Exercise Plasma to PV Interneuro

Score: 0.560 · neurodegeneration · 2026-04-14

## Mechanistic Overview Complement C1q Suppression as Mechanism Linking Exercise Plasma to PV Interneuron Protection sta

Nucleocytoplasmic Transport Disruption

Score: 0.520 · neurodegeneration · 2026-04-21

## Mechanistic Overview Nucleocytoplasmic Transport Disruption starts from the claim that modulating NUP107 within the d

SASP-Secreted MMP-9 from Senescent Microglia Disrupts TDP-43 Nuclear Retention L

Score: 0.511 · als · 2026-04-27

The hypothesis proposes that MMP-9 (matrix metalloproteinase-9), secreted via the senescence-associated secretory phenot

Nuclear Pore and Nucleocytoplasmic Transport Machinery as Gatekeepers

Score: 0.500 · neurodegeneration · 2026-04-21

## Mechanistic Overview Nuclear Pore and Nucleocytoplasmic Transport Machinery as Gatekeepers starts from the claim that

TDP-43 Phase Separation Destabilization Drives Cytoplasmic Aggregation

Score: 0.500 · neurodegeneration · 2026-05-03

Aberrant arginine methylation prevents TDP-43 liquid-liquid phase separation, promoting pathogenic aggregation. PRMT5-me

Plasma NfL Elevation Secondary to BBB-Associated Transport Dysfunction Enables L

Score: 0.485 · unknown disease · 2026-04-26

Neurofilament light chain (NfL) is released from damaged neurofilaments into the extracellular space, flowing into CSF a