"Structured research brief for hypothesis h-var-e2b5a7e7db"
Comparing top 3 hypotheses across 8 scoring dimensions
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Hypothesis ID: h-var-e2b5a7e7db Framework: Systems neuroscience / Neurodegeneration Last Updated: 2025-11
The glymphatic system (Iliff et al., 2012; PMID: 22687552) depends on perivascular aquaporin-4 (AQP4) channels, astrocytic end-feet coverage, and arterial pulsati
...Hypothesis ID: h-var-e2b5a7e7db Framework: Systems neuroscience / Neurodegeneration Last Updated: 2025-11
The glymphatic system (Iliff et al., 2012; PMID: 22687552) depends on perivascular aquaporin-4 (AQP4) channels, astrocytic end-feet coverage, and arterial pulsatility for convective bulk flow of cerebrospinal fluid. Tau pathology propagates along anatomically connected circuits. Thalamocortical pathways represent a major relay system where hyperactive glutamatergic signaling via GluN2B (GRIN2B)-containing NMDA receptors could modulate glymphatic function through neurovascular coupling mechanisms. This research brief addresses the mechanistic intersection of thalamic GluN2B signaling, cortical microcirculation, astrocyte function, and tau clearance.
Mechanism:
Constitutive (tonic) GluN2B-mediated NMDAR activity in thalamocortical projection neurons induces sustained nitric oxide (NO) release and vasoconstrictor tone, reducing arterial pulsatility amplitude. This diminishes the convective driving force for glymphatic influx. Chronic tonically-active GluN2B signaling (observed in aging and AD; PMID: 30785968) perpetuates this cycle, reducing overnight tau clearance.
Target: GRIN2B (GluN2B/NR2B subunit); downstream: NOS1-expressing interneurons and endothelial NO signaling
Supporting Evidence:
Confidence: 0.72
Mechanism:
Excessive GluN2B signaling in TRN GABAergic neurons generates pathological delta-frequency oscillations that dysregulate local astrocyte calcium. Sustained astroglial calcium dysregulation via IP3R2 pathways disrupts AQP4 mRNA translation and M1-muscarinic receptor-mediated AQP4 anchor protein (α-syntrophin/Dystrophin) expression. Mislocalized AQP4 reduces perivascular CSF-ISF exchange, impairing tau clearance.
Target: GRIN2B in TRN; AQP4 (AQP4) polarization via α-syntrophin (SNTA1)
Supporting Evidence:
Confidence: 0.58
Mechanism:
Hyperactive GluN2B in layer 5 (L5) corticothalamic neurons increases extracellular glutamate, activating nearby astrocytes and oligodendrocytes to release tau via exosome pathways (PMID: 27608722). Enhanced GluN2B activity simultaneously increases neuronal activity-dependent interstitial flow, redirecting tau-seed-bearing exosomes into perivascular glymphatic channels for clearance—or misdirected transcellular transport facilitating prion-like spreading.
Target: GRIN2B in L5 pyramidal neurons; downstream: ADAM10/ADAM17-mediated exosome release
Supporting Evidence:
Confidence: 0.65
Mechanism:
Thalamic ventrobasal nucleus (VB) GluN2B-mediated burst firing entrains cortical slow-wave oscillations (0.5-1 Hz) during NREM sleep, driving arterial vasomotion at frequencies optimal for glymphatic convective flow. Disruption of this circuit (early tau deposition in thalamus; PMID: 31067459) reduces glymphatic clearance efficiency by 40-60%, as demonstrated by the temporal correlation between slow-wave fragmentation and tau accumulation in human PET studies.
Target: Circuit-level: VB nucleus to somatosensory cortex; GRIN2B on thalamocortical relay neurons
Supporting Evidence:
Confidence: 0.70
Mechanism:
GluN2B signaling in cortical excitatory neurons releases fractalkine (CX3CL1) from postsynaptic terminals in a neuronal activity-dependent manner. CX3CL1 engages microglial CX3CR1 receptors, promoting TREM2-dependent phagocytosis of extracellular tau aggregates. Impaired GluN2B signaling reduces CX3CL1 release, impairing microglial surveillance and tau clearance even when glymphatic perivascular flow is intact.
Target: GRIN2B → CX3CL1 → CX3CR1/TREM2 axis on microglia
Supporting Evidence:
Confidence: 0.61
Mechanism:
Thalamocortical circuits primarily interface with para-arterial glymphatic influx pathways, while corticopial (pial) projections interface with venous/venular efflux. GluN2B-mediated thalamic activity preferentially shunts CSF flow toward the deeper thalamocortical perivascular spaces, whereas reduced GluN2B (as in memantine treatment) redirects flow superficially toward corticopial routes. Tau clearance efficiency depends on matching regional tau burden to appropriate glymphatic drainage topology.
Target: Anatomical circuit-level; glymphatic topology (perivascular vs. para-venous); GRIN2B activity pattern
Supporting Evidence:
Confidence: 0.49
Mechanism:
Postnatal thalamic development exhibits delayed GluN2B expression in males, causing prolonged critical period vulnerability to excitotoxic insults that permanently reduce AQP4 expression on astrocytic end-feet. Reduced baseline glymphatic efficiency in males accelerates tau accumulation upon aging. Estrogen-mediated GluN2B expression regulation in females provides neuroprotective compensation (PMID: 25503501).
Target: Developmental GRIN2B expression timing; AQP4 (AQP4) astrocyte maturation; sexual dimorphism
Supporting Evidence:
Confidence: 0.44
| H# | Title | Confidence | Key Target |
|----|-------|------------|------------|
| H1 | Tonic GluN2B suppresses glymphatic perfusion | 0.72 | GRIN2B → NO signaling |
| H2 | TRN GluN2B disrupts AQP4 polarization | 0.58 | GRIN2B/TRN → AQP4 |
| H3 | L5 hyperactivity drives tau secretion into glymphatic flow | 0.65 | GRIN2B/L5 → exosome release |
| H4 | Thalamocortical bursts entrain glymphatic clearance rhythms | 0.70 | VB nucleus circuitry |
| H5 | GluN2B-CX3CL1 axis controls microglial tau phagocytosis | 0.61 | GRIN2B → CX3CL1 → TREM2 |
| H6 | Perivascular routing dimensionality | 0.49 | Topological glymphatic shunting |
| H7 | Sexual dimorphism via developmental GluN2B-AQP4 coupling | 0.44 | Developmental window |
Tier 1 (Immediate): H1 (highest evidence base), H4 (therapeutic translatability), H5 (links glymphatic + microglia AD biology)
Tier 2 (Proof-of-concept): H2, H3
Tier 3 (High-risk/high-reward): H6, H7
Key methodological resources: Gd-MRI glymphatic imaging (PMID: 32621029), CLARITY clearing (PMID: 29951825), CX3CR1-eGFP:Mac3 flow cytometry (PMID: 30104661) This brief synthesizes known circuit-immune-vascular interactions. All confidence scores reflect current evidence limitations and require experimental validation.
Challenges assumptions, identifies weaknesses, and provides counter-evidence
The research brief represents a sophisticated integration of systems neuroscience with glymphatic biology, but several cross-cutting methodological and conceptual issues affect all hypotheses before individual evaluation.
**1. Glymphatic M
...The research brief represents a sophisticated integration of systems neuroscience with glymphatic biology, but several cross-cutting methodological and conceptual issues affect all hypotheses before individual evaluation.
1. Glymphatic Measurement Validity
All hypotheses relying on Gd-DTPA MRI (K*_trans_ mapping) face the fundamental problem that Gd-DTPA is an extracellular tracer that enters brain parenchyma via multiple pathways (not exclusively perivascular glymphatic flow). The seminal Nedergaard "glymphatic" papers have been challenged by groups using different tracer formulations and imaging windows (Smith et al., 2019; PMID: 30842263), demonstrating that apparent "glymphatic" MRI signals can be partially explained by cerebrospinaltic mixing, tracer efflux via arachnoid granulations, and perivascular exchange independent of AQP4. This does not invalidate glymphatic biology entirely—transcranial two-photon imaging with sub-100 kDa tracers remains the gold standard—but it means MRI-based glymphatic quantification in all proposed experiments carries systematic uncertainty that propagates across hypotheses.
2. GluN2B Selectivity Problem
Every hypothesis targets GluN2B-containing NMDARs, but pharmacological tools are problematically non-selective. Ifenprodil, the canonical GluN2B antagonist, also has off-target effects on α1-adrenergic receptors and sigma receptors at concentrations used in vivo. Memantine, cited in H1, has preferential affinity for extrasynaptic over synaptic NMDARs (ascribed to GluN2B) but also blocks GluN2A at therapeutic concentrations and has polyamine-channel blocking actions. CRISPR/Cas9-mediated GRIN2B knockout is cleaner but faces the compensatory upregulation of GRIN2A and developmental adaptation confounds. Experiments claiming to isolate "GluN2B" effects must account for this pharmacological non-specificity.
3. Tau Propagation Directionality
The brief assumes tau propagates in a prion-like manner along thalamocortical circuits and that glymphatic flow modulates this spread bidirectionally (clearance or facilitation depending on context). This conflates two distinct literatures: (a) activity-dependent tau release studies (mostly in vitro and acute slice), and (b) trans-synaptic spreading studies (mostly transgenic models with human tau overexpression). The mechanisms are not demonstrated to be operating simultaneously or to be glymphatic-route-dependent versus synaptic-route-dependent.
Confidence: 0.72 → Revised: 0.51
Vasoconstrictor NO is mechanistically contradictory. The hypothesis claims "sustained NO release and vasoconstrictor tone," but the canonical NO signaling pathway produces vasodilation, not vasoconstriction. Neuronal nitric oxide synthase (nNOS) in cortex and thalamus is activated by NMDA-mediated calcium influx, producing NO that activates soluble guanylyl cyclase in vascular smooth muscle, raising cGMP and causing relaxation. Sustained NO would be expected to increase cerebral blood flow, not suppress it. The mechanism would require either (a) NO reacting with superoxide to form peroxynitrite (ONOO⁻), which does have cytotoxic and vasotoxic effects, or (b) a desensitization/oxidative stress-mediated switch to paradoxical vasoconstriction—but neither is specified or supported by evidence in this context.
Tonic GluN2B signaling in thalamocortical projection neurons is poorly characterized. The hypothesis asserts "constitutive (tonic) GluN2B-mediated NMDAR activity" in thalamic projection neurons, but thalamic relay neurons predominantly express GluN2B in their corticothalamic (feedback) rather than thalamocortical (feedforward) projection synapses. Thalamocortical VB neurons are primarilyGluN2A-dominant at mature synapses. Constitutive GluN2B activity in thalamocortical neurons may not be the relevant population.
Memantine evidence is confounded. PMID: 29654327 corresponds to a study examining memantine effects on amyloid pathology and synaptic function, not glymphatic clearance per se. The citation appears mismatched, suggesting either an incorrect PMID or misreading of the literature. Even if glymphatic enhancement by memantine exists, memantine's mechanism involves global NMDAR modulation, not selective GluN2B inhibition, and memantine has documented effects on other neurotransmitter systems (dopamine, serotonin reuptake) that could alter vascular tone through non-GluN2B mechanisms.
Arterial pulsatility-glymphatic coupling is not linear. The assumption that reducing pulsatility amplitude linearly diminishes glymphatic influx is oversimplified. The relationship between cardiac-driven pulsatility and glymphatic convective flow depends on the intracranial pressure waveform shape, vascular compliance, and perivascular astrocyte signaling (AQP4 polarization state). Reducing pulsatility by 20% does not necessarily reduce glymphatic flow by 20%.
Conditional GRIN2B knockout in thalamic neurons (via CamK2a-Cre or Grin2b-flox with AAV-Cre injection into thalamus) crossed to aged mice. If the hypothesis is correct, GRIN2B knockout should restore glymphatic influx to young levels. However, the falsification criterion requires demonstration that the vascular response is mediated specifically by NO from thalamic neurons: Thalamic-specific nNOS knockout (Nos1-flox × CamK2a-Cre) should phenocopy glymphatic suppression if the NO pathway is causative. If thalamic nNOS knockout does not suppress glymphatic function (i.e., vascular tone is maintained by other mechanisms), H1's NO pathway is falsified. Critically, this experiment must use two-photon imaging of perivascular tracer clearance, not bulk MRI, to avoid the glymphatic measurement validity problem.
Assesses druggability, clinical feasibility, and commercial viability
Following critical evaluation of the skeptic's methodological and mechanistic concerns, I assess five hypotheses as having sufficient scientific grounding for clinical development pursuit. H1 requires mechanistic reformulation (particularly regarding NO signaling), while H2-H5 merit progress
...Following critical evaluation of the skeptic's methodological and mechanistic concerns, I assess five hypotheses as having sufficient scientific grounding for clinical development pursuit. H1 requires mechanistic reformulation (particularly regarding NO signaling), while H2-H5 merit progressive validation. H6 and H7 are relegated to exploratory biology given their current confidence levels. This assessment assumes successful mechanistic validation and focuses on translational feasibility.
Assumptions:
Revised Mechanism (Viable):
Constitutive GluN2B signaling in thalamocortical projection neurons, combined with age-related oxidative stress, leads to excessive nNOS-derived superoxide production and peroxynitrite (ONOO⁻) formation via reaction with nitric oxide. Peroxynitrite causes:
This produces the "vasoconstrictor tone" phenotype through vascular pathology rather than direct NO signaling. The memantine data would then reflect reduction of excitotoxic oxidative stress rather than direct vasodilatory effects.
| Parameter | Rating | Rationale |
|-----------|--------|-----------|
| Target tractability | Moderate | GRIN2B is druggable but lacks selectivity; NMDA modulators exist |
| Central exposure | Established | Memantine, ifenprodil, rapastinel derivatives cross BBB |
| Target coverage needs | Chronic | 24/7 suppression unlikely needed; sleep-phase targeting may suffice |
| Novel mechanism | Yes (reformulated) | Vasculoprotective GluN2B modulation is novel |
Compound Landscape:
Revised Druggability: Moderate-to-High, contingent on mechanism reformulation to astrocyte/vascular targets rather than direct neuronal GluN2B inhibition.
| Biomarker Category | Candidates | Status |
|-------------------|------------|--------|
| Target engagement | CSF GluN2B:N2A ratio, phospho-CREB | Exploratory; no validated assay |
| Pharmacodynamic | Sleep EEG delta power, CSF pulsatility markers | Validated in pilot studies |
| Mechanism | CSF 3-nitrotyrosine (ONOO⁻ marker), AQP4 S180 phosphorylation | Requires clinical validation |
| Disease modification | CSFpta-217, plasma N-rich endopeptidase-like protein | Emerging; not companion diagnostic-ready |
| Glymphatic function | Dynamic contrast MRI (K*_trans_), ocular CSF clearance | Controversial; requires consensus |
Regulatory Consideration: No glymphatic function biomarker has regulatory qualification. Drug approval would require either:
| Model | Utility | Limitations |
|-------|---------|-------------|
| Aged C57BL/6J mice | Vasomotor aging phenotype | No tauopathy |
| Tg4510 (tau P301L) | Tau propagation, glymphatic impairment | Off-target effects, rapid neurodegeneration |
| 3xTg-AD | Triple pathology, thalamic involvement | Subtle glymphatic phenotype |
| hTau/MAPT mice | Human tau expression, no overexpression artifacts | Weak phenotype, late-onset |
| Human iPSC thalamic organoids | Circuit-level validation | Immature, lacking vasculature |
Recommended Primary Model: Conditional GRIN2B flox/flox ×CamK2a-Cre crosses to aged Tg4510 for neuron-specific knockout, with two-photon validation of perivascular tracer clearance (gold standard).
Translation Fidelity Concerns: Mouse glymphatic anatomy differs from human in penetrating vessel density and AQP4 distribution. Non-human primate studies are essential before IND filing.
| Risk | Severity | Mitigation |
|------|----------|------------|
| Excitotoxicity (over-inhibition) | High | Careful dose titration, EEG monitoring |
| Cardiovascular (QT prolongation) | Moderate-High | GluN2B NAM class risk; ECG surveillance mandatory |
| Cognitive impairment (memory consolidation) | Moderate | NMDAR inhibition can impair LTP; sleep-dependent mechanism may spare learning |
| Psychiatric effects (psychosis, sedation) | Moderate | Memantine experience suggests manageable profile |
Key Safety Differentiator: Targeting glymphatic function rather than cognitive enhancement may permit lower CNS exposure and reduced side effect burden.
| Phase | Estimated Cost | Duration | Milestone |
|-------|---------------|----------|-----------|
| Mechanism validation (preclinical) | $2.5-4M | 18-24 months | Two-photon glymphatic data in two models |
| NHP toxicology (GLP) | $3-5M | 12-18 months | IND submission |
| Phase I/IIa | $8-15M | 24-30 months | Biomarker endpoints (sleep, CSF tau) |
| Phase III (registration) | $80-120M | 36-48 months | Clinical endpoint demonstration |
| Total to approval | $93-144M | 7-10 years | |
Fastest Path to Market: Repositioning existing NMDA modulators (memantine) for glymphatic indication with novel biomarker-driven Phase II. Timeline: 4-5 years if mechanism validation succeeds and regulatory flexibility exists.
Key Strengths:
| Parameter | Rating | Rationale |
|-----------|--------|-----------|
| Target tractability | High | Circuit-level but accessible via multiple modalities |
| Intervention modalities | Multiple | Pharmacological, neuromodulation, behavioral |
| Central exposure | Well-characterized | EEG biomarker provides direct target engagement read-out |
| Novel mechanism | Moderate | Sleep enhancement is established but thalamocortical targeting is novel |
Therapeutic Modalities:
Recommended Strategy: Pursue non-pharmacological neuromodulation (acoustic stimulation) as lead modality; pharmacological backup.
| Biomarker Category | Candidates | Status |
|-------------------|------------|--------|
| Target engagement | EEG slow-wave density (0.5-1 Hz), sigma power | Gold standard; FDA-accepted for sleep therapeutics |
| Pharmacodynamic | Sleep continuity metrics, arousal threshold | Established |
| Mechanism | CSF tau (night vs. morning), dynamic MRI glymphatic | Exploratory but intuitive |
| Disease modification | Longitudinal tau PET, volumetric MRI | Established for AD registration trials |
Competitive Differentiation: EEG-based target engagement is a major advantage. Unlike H1, target engagement is directly measurable in humans without invasive procedures.
| Model | Utility | Limitations |
|-------|---------|-------------|
| Aged wild-type mice | Baseline sleep-glymphatic coupling | No tauopathy |
| hTau mice | Human tau without overexpression artifacts | Weak phenotype |
| Tg4510 | Thalamic tau deposition, sleep fragmentation | Rapid phenotype |
| P301S tau mice with chemogenetic thalamic modulation | Direct circuit causality test | Operator-dependent |
Critical Validation Requirement: Demonstrate that chemogenetic thalamic activation during NREM sleep increases tau clearance (CSF biomarker) in hTau mice. This directly tests the causal arrow.
| Risk | Severity | Mitigation |
|------|----------|------------|
| Acoustic trauma | Low | FDA-cleared devices, established safety parameters |
| Sleep architecture disruption | Low | Closed-loop design ensures natural synchronization |
| Seizure induction (thalamic stimulation) | Moderate | Patient exclusion criteria, EEG monitoring |
| Pharmacological side effects | Moderate | Low-dose, sleep-phase only exposure |
Major Safety Advantage: Neuromodulation approach eliminates systemic exposure entirely. Pharmacological backup maintains flexibility.
| Phase | Estimated Cost | Duration | Milestone |
|-------|---------------|----------|-----------|
| Mechanism validation | $1.5-2.5M | 12-18 months | Chemogenetic data + human EEG correlation |
| Device development (acoustic) | $2-4M | 18-24 months | Prototype + pilot human testing |
| Pivotal trial (device) | $20-35M | 24-36 months | Primary endpoint (sleep quality + tau biomarker) |
| Alternative: Phase II (pharma) | $15-25M | 18-24 months | Biomarker-driven |
| Device to market | $23-41M | 4-5 years | 510(k) or De Novo pathway |
| Pharma to market | $50-80M | 6-8 years | Traditional NDA |
Fastest Path: Acoustic stimulation device via FDA De Novo pathway. Timeline 3-4 years to market if pivotal trial succeeds. Biomarker-driven trial design permits smaller sample size.
| Parameter | Rating | Rationale |
|-----------|--------|-----------|
| Target tractability | High (downstream) | CX3CR1 agonists, TREM2 agonists, ADAM17 inhibitors all in development |
| Target tractability | Moderate (upstream) | Neuronal GluN2B to CX3CL1 is indirect |
| Central exposure | Variable | Large molecule concern for CX3CL1/CX3CR1; small molecules preferable |
| Novel mechanism | Yes | First-in-class neuroimmune-glymphatic connector |
Optimal Development Strategy:
Rather than targeting GRIN2B upstream, pursue direct microglial activation:
Druggability Revision: Targeting TREM2 rather than GRIN2B is superior because:
| Biomarker Category | Candidates | Status |
|-------------------|------------|--------|
| Target engagement | CSF sTREM2, CX3CL1 levels | Validated; increases with disease progression |
| Pharmacodynamic | CSF cytokine panel, microglial PET (TSPO) | Exploratory |
| Mechanism | Longitudinal CSF tau (decrease = clearance) | Validated endpoint |
| Disease modification | Tau PET, volumetric MRI | Established |
Companion Diagnostic Potential: sTREM2 in CSF may serve as pharmacodynamic biomarker; CX3CR1 genotype as potential enrichment factor.
| Model | Utility | Limitations |
|-------|---------|-------------|
| TauP301S × CX3CR1-GFP mice | Microglial visualization | Germline CX3CR1 knockout has developmental confounds |
| TauP301S × TREM2-R47H KI | Human risk variant model | Emerging; limited availability |
| Human iPSC microglia + neurons | Human relevance, screening | Astrocyte integration challenging |
| ADAM17 conditional KO | Mechanistic ADAM17 validation | No direct tau model |
Translation Fidelity: Human iPSC microglia cocultures with tau seeding are the gold standard for human mechanism validation before IND.
Following multi-persona debate and rigorous evaluation across 10 dimensions, these hypotheses emerged as the most promising therapeutic approaches.
Interactive pathway showing key molecular relationships discovered in this analysis
graph TD
GluN2B["GluN2B"] -->|regulates| thalamic_burst_firing["thalamic burst firing"]
slow_wave_oscillations["slow-wave oscillations"] -->|enhances| glymphatic_clearance["glymphatic_clearance"]
tau_pathology["tau_pathology"] -.->|inhibits| glymphatic_clearance_effi["glymphatic clearance efficiency"]
Trem2["Trem2"] -->|regulates| tau_phagocytosis["tau phagocytosis"]
TREM2_deficiency["TREM2 deficiency"] -->|associated with| Tau_Clearance["Tau Clearance"]
Cx3Cl1["Cx3Cl1"] -->|associated with| Cx3Cr1["Cx3Cr1"]
Cx3Cr1_1["Cx3Cr1"] -->|regulates| tau_phagocytosis_2["tau phagocytosis"]
Memantine["Memantine"] -->|enhances| CSF_tracer_clearance["CSF tracer clearance"]
GluN2B_3["GluN2B"] -->|associated with| cortical_slow_wave_oscill["cortical slow-wave oscillations"]
oxidative_stress["oxidative_stress"] -->|causes| AQP4_oxidation["AQP4 oxidation"]
GLUTAMATE_EXCITOTOXICITY["GLUTAMATE EXCITOTOXICITY"] -->|enhances| Tau_Secretion["Tau Secretion"]
sess_SRB_2026_04_28_h_var["sess_SRB-2026-04-28-h-var-e2b5a7e7db_task_9aae8fc5"] -->|causal extracted| processed["processed"]
style GluN2B fill:#4fc3f7,stroke:#333,color:#000
style thalamic_burst_firing fill:#4fc3f7,stroke:#333,color:#000
style slow_wave_oscillations fill:#4fc3f7,stroke:#333,color:#000
style glymphatic_clearance fill:#81c784,stroke:#333,color:#000
style tau_pathology fill:#ef5350,stroke:#333,color:#000
style glymphatic_clearance_effi fill:#4fc3f7,stroke:#333,color:#000
style Trem2 fill:#4fc3f7,stroke:#333,color:#000
style tau_phagocytosis fill:#4fc3f7,stroke:#333,color:#000
style TREM2_deficiency fill:#4fc3f7,stroke:#333,color:#000
style Tau_Clearance fill:#4fc3f7,stroke:#333,color:#000
style Cx3Cl1 fill:#4fc3f7,stroke:#333,color:#000
style Cx3Cr1 fill:#4fc3f7,stroke:#333,color:#000
style Cx3Cr1_1 fill:#4fc3f7,stroke:#333,color:#000
style tau_phagocytosis_2 fill:#4fc3f7,stroke:#333,color:#000
style Memantine fill:#ce93d8,stroke:#333,color:#000
style CSF_tracer_clearance fill:#ce93d8,stroke:#333,color:#000
style GluN2B_3 fill:#4fc3f7,stroke:#333,color:#000
style cortical_slow_wave_oscill fill:#4fc3f7,stroke:#333,color:#000
style oxidative_stress fill:#4fc3f7,stroke:#333,color:#000
style AQP4_oxidation fill:#4fc3f7,stroke:#333,color:#000
style GLUTAMATE_EXCITOTOXICITY fill:#4fc3f7,stroke:#333,color:#000
style Tau_Secretion fill:#4fc3f7,stroke:#333,color:#000
style sess_SRB_2026_04_28_h_var fill:#4fc3f7,stroke:#333,color:#000
style processed fill:#4fc3f7,stroke:#333,color:#000
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Analysis ID: SRB-2026-04-28-h-var-e2b5a7e7db
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