🧪 Hypotheses

therapeutic 0.84

APOE4-Specific Lipidation Enhancement Therapy

🧬 APOE 🏥 Alzheimer's disease

✅ 0.00 ✨ 0.00 💥 0.00

## Molecular Mechanism and Rationale...

therapeutic 0.71

Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via direct PV interneuron recruitm

🧬 PVALB 🏥 Alzheimer's disease

✅ 0.88 ✨ 0.80 💥 0.82

**Background and Rationale**...

mechanistic 0.70

SASP-Mediated Complement Cascade Amplification

🧬 C1Q/C3 🏥 neurodegeneration

✅ 0.75 ✨ 0.85 💥 0.80

**SASP-Mediated Complement Cascade Amplification in Alzheimer's Disease**...

unknown 0.70

Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Partially Irreversible

🧬 APP/PSEN1 (Aβ production), CHAT (cholinergic synthesis) 🏥 N/A

✅ 0.60 ✨ 0.55 💥 0.85

...

therapeutic 0.70

Closed-loop tACS targeting EC-II SST interneurons to block tau propagation and restore perforant-path gamma gating in AD

🧬 SST 🏥 Alzheimer's disease

✅ 0.86 ✨ 0.78 💥 0.82

## Molecular Mechanism and Rationale...

therapeutic 0.70

Closed-loop focused ultrasound targeting EC-II SST interneurons to restore gamma gating and block tau propagation in AD

🧬 SST 🏥 Alzheimer's disease

✅ 0.87 ✨ 0.79 💥 0.81

## Molecular Mechanism and Rationale...

therapeutic 0.69

Hippocampal CA3-CA1 synaptic rescue via DHHC2-mediated PSD95 palmitoylation stabilization

🧬 BDNF 🏥 Alzheimer's disease

✅ 0.70 ✨ 0.82 💥 0.83

## Molecular Mechanism and Rationale...

mechanistic 0.69

TREM2-Dependent Microglial Senescence Transition

🧬 TREM2 🏥 neurodegeneration

✅ 0.72 ✨ 0.78 💥 0.91

**Background and Rationale**...

therapeutic 0.69

Closed-loop transcranial focused ultrasound with 40Hz gamma entrainment to restore hippocampal-cortical synchrony via se

🧬 PVALB 🏥 Alzheimer's disease

✅ 0.00 ✨ 0.00 💥 0.00

This hypothesis combines the spatial precision of transcranial focused ultrasound (tFUS) with the proven efficacy of 40Hz gamma entrainment to create ...

therapeutic 0.68

Gamma entrainment therapy to restore hippocampal-cortical synchrony

🧬 SST 🏥 Alzheimer's disease

✅ 0.88 ✨ 0.78 💥 0.80

**Gamma Entrainment Therapy for Alzheimer's Disease: Circuit-Level Intervention**...

therapeutic 0.68

Hippocampal CA3-CA1 circuit rescue via neurogenesis and synaptic preservation

🧬 BDNF 🏥 Alzheimer's disease

✅ 0.72 ✨ 0.68 💥 0.78

**Molecular Mechanism and Rationale**...

unknown 0.68

H2: Indole-3-Propionate (IPA) as the Actual Neuroprotective Effector

🧬 PXR (NR1I2), IDO1 🏥 neurodegeneration

✅ 0.80 ✨ 0.88 💥 0.75

# H2: Indole-3-Propionate (IPA) as the Actual Neuroprotective Effector Downstream of GLP-1 Signaling...

unknown 0.67

CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Window Identification

🧬 sTREM2/membrane-TREM2/ADAM10 🏥 neuroimmunology

✅ 0.85 ✨ 0.60 💥 0.88

# CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Window Identification...

therapeutic 0.67

Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and block tau propagation via perforant path i

🧬 PVALB 🏥 Alzheimer's disease

✅ 0.87 ✨ 0.78 💥 0.81

## Molecular Mechanism and Rationale...

mechanistic 0.67

Nutrient-Sensing Epigenetic Circuit Reactivation

🧬 SIRT1 🏥 neurodegeneration

✅ 0.95 ✨ 0.70 💥 0.85

**Molecular Mechanism and Rationale**...

therapeutic 0.67

Beta-frequency entrainment therapy targeting PV interneuron-astrocyte coupling for tau clearance

🧬 SST 🏥 Alzheimer's disease

✅ 0.85 ✨ 0.82 💥 0.82

## Molecular Mechanism and Rationale...

mechanistic 0.66

Transcriptional Autophagy-Lysosome Coupling

🧬 FOXO1 🏥 neurodegeneration

✅ 0.75 ✨ 0.80 💥 0.78

**Transcriptional Autophagy-Lysosome Coupling via FOXO1-TFEB Coordination**...

unknown 0.66

Stathmin-2 Splice Switching to Prevent Axonal Degeneration Across the ALS-FTD-AD Spectrum

🧬 STMN2 (stathmin-2), PTBP1/PTBP2 🏥 neurodegeneration

✅ 0.80 ✨ 0.70 💥 0.88

TDP-43 loss-of-function causes inclusion of a poison exon in STMN2 mRNA, leading to motor neuropathy and contributing to hippocampal axonal dysfunctio...

mechanistic 0.66

ACSL4-Driven Ferroptotic Priming in Disease-Associated Microglia

🧬 ACSL4 🏥 Alzheimer's Disease

✅ 0.75 ✨ 0.85 💥 0.85

## 1. Molecular Mechanism and Rationale...

therapeutic 0.66

Closed-loop tACS targeting EC-II parvalbumin interneurons to restore gamma rhythmogenesis and block tau AIS disruption i

🧬 PVALB 🏥 Alzheimer's disease

✅ 0.86 ✨ 0.79 💥 0.80

## Molecular Mechanism and Rationale...

unknown 0.66

STMN2 Restoration as a Prerequisite for Axon Growth After TDP-43 Clearance

🧬 STMN2 🏥 neurodegeneration

✅ 0.85 ✨ 0.70 💥 0.82

Stathmin-2-Dependent Microtubule Destabilization Reversal Enables Motor Axon Sprouting. The observed functional recovery requires restoration of STMN2...

unknown 0.65

Temporal SPP1 Inhibition During Critical Windows

🧬 SPP1 🏥 neuroinflammation

✅ 0.70 ✨ 0.75 💥 0.80

# Temporal SPP1 Inhibition During Critical Windows: Mechanistic Framework and Therapeutic Rationale...

therapeutic 0.65

Selective Acid Sphingomyelinase Modulation Therapy

🧬 SMPD1 🏥 neurodegeneration

✅ 0.90 ✨ 0.70 💥 0.85

**Overview**...

unknown 0.65

Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone Deficiency to Neuroinflammation

🧬 HCAR2 🏥 neurodegeneration

✅ 0.82 ✨ 0.70 💥 0.75

Beyond serving as metabolic fuel, β-hydroxybutyrate (BHB) signals through hydroxycarboxylic acid receptor 2 (HCAR2/GPR109A) on astrocytes to suppress ...

therapeutic 0.64

Dual-Receptor Antibody Shuttling

🧬 N/A 🏥 Alzheimer's disease

✅ 0.00 ✨ 0.00 💥 0.00

Dual-Receptor Antibody Shuttling is a therapeutic strategy targeting dual receptor mechanisms for antibody delivery across the blood-brain barrier. Th...

therapeutic 0.64

Closed-loop transcranial alternating current stimulation to restore hippocampal-prefrontal gamma synchrony via PV intern

🧬 SST 🏥 Alzheimer's disease

✅ 0.88 ✨ 0.78 💥 0.81

## Molecular Mechanism and Rationale...

mechanistic 0.64

TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegeneration

🧬 TREM2 🏥 neurodegeneration

✅ 0.00 ✨ 0.00 💥 0.00

**Background and Rationale** TREM2 variants represent major genetic risk factors for Alzheimer's disease, with loss-of-function mutations increasing d...

mechanistic 0.64

SASP-Driven Microglial Metabolic Reprogramming in Synaptic Phagocytosis

🧬 HK2/PFKFB3 🏥 neurodegeneration

✅ 0.70 ✨ 0.80 💥 0.75

## Molecular Mechanism...

unknown 0.64

TREM2-Dependent Microglial Phagocytosis Acts as a Strain Selection Filter

🧬 TREM2 🏥 neurodegeneration

✅ 0.78 ✨ 0.72 💥 0.80

TREM2 on microglia normally clears tau pathology, but sTREM2 signaling mediates early synaptic injury and may paradoxically facilitate strain selectio...

therapeutic 0.63

Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via cholecystokinin interneuron ne

🧬 CCK 🏥 Alzheimer's disease

✅ 0.00 ✨ 0.00 💥 0.00

**Background and Rationale**...