🧪 Hypotheses

mechanistic 0.96

GluN2B-Mediated Thalamocortical Control of Glymphatic Tau Clearance

🧬 GRIN2B 🏥 neuroscience 📖 30🏛 4

✅ 0.85 ✨ 0.78 💥 0.82

## Mechanistic Overview...

mechanistic 0.95

Cortico-Striatal Synchrony Restoration via NMDA Modulation

🧬 GRIN2B 🏥 neuroscience 📖 15🏛 3

✅ 0.78 ✨ 0.34 💥 0.80

**Molecular Mechanism and Rationale**...

mechanistic 0.94

Microglial-Mediated Tau Clearance Dysfunction via TREM2 Receptor Impairment

🧬 MAPT 🏥 neuroscience 📖 17🏛 3

✅ 0.77 ✨ 0.56 💥 0.79

**Molecular Mechanism and Rationale**...

combination 0.86

Glymphatic-Mediated Tau Clearance Dysfunction

🧬 MAPT 🏥 neuroscience 📖 31🏛 3

✅ 0.68 ✨ 0.85 💥 0.78

## Mechanistic Overview...

combination 0.86

TREM2-Mediated Microglial Dysfunction Disrupts Perivascular Tau Clearance

🧬 TREM2 🏥 neuroscience 📖 28🏛 4

✅ 0.00 ✨ 0.49 💥 0.00

## Mechanistic Overview...

unknown 0.83

Ketone Utilization Index as Metabolic Flexibility Biomarker

🧬 HMGCS2 🏥 translational-neuroscience 📖 46🏛 1

✅ 0.75 ✨ 0.85 💥 0.65

## Mechanistic Overview...

combination 0.83

Microglial-Mediated Tau Clearance Dysfunction via TREM2 Signaling

🧬 TREM2 🏥 neuroscience 📖 2🏛 3

✅ 0.70 ✨ 0.65 💥 0.85

## Mechanistic Overview...

unknown 0.82

Inhibiting Heparan Sulfate Proteoglycan Receptor-Mediated Neuronal Tau Uptake

🧬 SULF1/SULF2 🏥 neuroscience 📖 0🏛 1

✅ 0.72 ✨ 0.65 💥 0.82

**Molecular Mechanism and Rationale**...

unknown 0.81

Thalamocortical Feedforward Inhibition Imposes Rhythm on Glymphatic Waste Clearance Windows

🧬 GRIN2B (VB thalamocortical relay neurons); circuit-level target 🏥 neuroscience 📖 20🏛 1

✅ 0.82 ✨ 0.65 💥 0.88

Thalamic ventrobasal nucleus GluN2B-mediated burst firing entrains cortical slow-wave oscillations (0.5-1 Hz) during NREM sleep, driving arterial vaso...

unknown 0.78

Biphasic Ketogenic Intervention Protocol

🧬 HMGCS2 🏥 metabolic-neuroscience 📖 8🏛 1

✅ 0.60 ✨ 0.80 💥 0.80

## Mechanistic Overview...

combination 0.77

Dual-Circuit Tau Vulnerability Cascade

🧬 MAPT 🏥 neuroscience 📖 17🏛 3

✅ 0.65 ✨ 0.70 💥 0.72

## Mechanistic Overview...

combination 0.77

Thalamocortical Synchrony Restoration via NMDA Modulation

🧬 GRIN2B 🏥 neuroscience 📖 10🏛 3

✅ 0.90 ✨ 0.70 💥 0.70

## Mechanistic Overview...

unknown 0.77

Enhancing Microglial Phagocytosis of Extracellular Tau via TREM2 Activation

🧬 TREM2 🏥 neuroscience 📖 0🏛 2

✅ 0.85 ✨ 0.58 💥 0.80

**Molecular Mechanism and Rationale**...

unknown 0.76

Selective LXRβ agonists restore ABCA1/ABCG1 expression and APOE lipidation in APOE4 astrocytes, normalizing cholesterol

🧬 NR1H2 (LXRβ), ABCA1, ABCG1 🏥 neuroscience 📖 8🏛 1

✅ 0.74 ✨ 0.62 💥 0.85

**Molecular Mechanism and Rationale**...

unknown 0.76

GluN2B-CX3CL1 Axis Controls Microglial Tau Phagocytosis

🧬 GRIN2B → CX3CL1 → CX3CR1/TREM2 axis 🏥 neuroscience 📖 0🏛 1

✅ 0.75 ✨ 0.75 💥 0.82

GluN2B signaling in cortical excitatory neurons releases fractalkine (CX3CL1) via activity-dependent TACE/ADAM17 shedding. CX3CL1 engages microglial C...

combination 0.76

Cholinergic Basal Forebrain-Hippocampal Circuit Protection

🧬 MAPT 🏥 neuroscience 📖 17🏛 3

✅ 0.70 ✨ 0.65 💥 0.80

## **Molecular Mechanism and Rationale**...

unknown 0.76

APOE4 astrocytes exhibit impaired cholesterol efflux via ABCA1/ABCG1 transporters, driving intracellular lipid droplet a

🧬 ABCA1, ABCG1 🏥 neuroscience 📖 8🏛 1

✅ 0.65 ✨ 0.58 💥 0.82

## Mechanistic Overview...

therapeutic 0.75

Dopaminergic Ventral Tegmental-Hippocampal Circuit Protection

🧬 MAPT 🏥 neuroscience 📖 17🏛 3

✅ 0.70 ✨ 0.75 💥 0.72

## Mechanistic Overview...

unknown 0.72

TDP-43 condensation thermodynamics as a therapeutic target and biomarker for nuclear-cytoplasmic compartmentalization

🧬 TARDBP (TDP-43 protein); IPO4/IP09 (nuclear import receptors as secondary targets) 🏥 neuroscience 📖 8🏛 1

✅ 0.68 ✨ 0.80 💥 0.72

FRAP-based measurement of TDP-43 liquid-liquid phase separation state provides a continuous biomarker of nuclear-cytoplasmic compartmentalization. End...

unknown 0.71

Creatine Kinase System Capacity as Neural Energy Reserve Biomarker

🧬 CKB 🏥 translational-neuroscience 📖 8🏛 1

✅ 0.50 ✨ 0.65 💥 0.60

## Mechanistic Overview...

unknown 0.70

Astrocyte-Neuron Metabolic Coupling Titration

🧬 BDH1 🏥 metabolic-neuroscience 📖 8🏛 1

✅ 0.50 ✨ 0.70 💥 0.70

**Molecular Mechanism and Rationale**...

unknown 0.70

GluN2B Tonic Activity Suppresses Glymphatic Perfusion Via Vasomotion Dysregulation

🧬 GRIN2B (thalamocortical projection neurons); downstream: NOS1, AQP4 🏥 neuroscience 📖 0🏛 1

✅ 0.72 ✨ 0.70 💥 0.78

REVISED MECHANISM (post-Skeptic critique): Constitutive GluN2B signaling combined with age-related oxidative stress leads to excessive nNOS-derived su...

unknown 0.68

GLUT1-Mediated Glucose Flux Coefficient as Neuroprotection Indicator

🧬 SLC2A1 🏥 translational-neuroscience 📖 7🏛 1

✅ 0.30 ✨ 0.75 💥 0.70

**Molecular Mechanism and Rationale**...

unknown 0.68

TREM2 R47H variant synergizes with APOE4 to collapse microglial lipid clearance capacity, causing extracellular lipid ac

🧬 TREM2, APOE 🏥 neuroscience 📖 8🏛 1

✅ 0.58 ✨ 0.88 💥 0.78

## **Molecular Mechanism and Rationale**...

unknown 0.68

Cortical Layer 5 Pyramidal Neuron GluN2B-Mediated Hyperactivity Drives Tau Secretion Into Glymphatic Flow

🧬 GRIN2B (L5 pyramidal neurons); downstream: ADAM10/ADAM17 🏥 neuroscience 📖 0🏛 1

✅ 0.68 ✨ 0.68 💥 0.72

Hyperactive GluN2B in L5 corticothalamic neurons increases extracellular glutamate, activating astrocytes and oligodendrocytes to release tau via exos...

unknown 0.68

TFEB-mediated transcriptional upregulation of lysosomal genes as a therapeutic strategy for AD

🧬 TFEB (TFEC) 🏥 neuroscience 📖 8🏛 1

✅ 0.55 ✨ 0.68 💥 0.75

**Molecular Mechanism and Rationale**...

unknown 0.68

Dynamic Lactate-Pyruvate Ratio as Therapeutic Stratification Biomarker

🧬 SLC16A1 🏥 translational-neuroscience 📖 6🏛 1

✅ 0.45 ✨ 0.80 💥 0.55

## Mechanistic Overview...

therapeutic 0.68

Microglial TREM2-Mediated Tau Phagocytosis Impairment

🧬 MAPT 🏥 neuroscience 📖 17🏛 3

✅ 0.00 ✨ 0.00 💥 0.00

**Molecular Mechanism and Rationale**...

mechanistic 0.67

Astrocytic-Mediated Tau Clearance Dysfunction via TREM2 Signaling

🧬 TREM2 🏥 neuroscience 📖 18🏛 3

✅ 0.00 ✨ 0.00 💥 0.00

## **Molecular Mechanism and Rationale**...

combination 0.67

Locus Coeruleus-Hippocampal Circuit Protection

🧬 MAPT 🏥 neuroscience 📖 14🏛 3

✅ 0.50 ✨ 0.75 💥 0.85

## Mechanistic Overview...