Notebook Artifact Registry

Computational analysis artifacts linked to analyses and knowledge graph entities

AllAPOE4AgingAllen InstituteAlzheimer'sCRISPRCircuit AnalysisCross-Age AnalysisEpigeneticsGene ExpressionImmune ResponseMicrogliaMouse ModelNeural DynamicsNeurodegenerationNeuroinflammationProtein PropagationSEA-ADSenescent CellsSenolyticsStructural BiologyTauTherapeutics[]agingalzheimersanalysisartifactastrocytesautobiomarkerscell-typescidraftepigeneticsforge-toolsgene-expressionhypothesis-analysisknowledge-gaplipid-raftsmicroglianeurodegenerationneuroinflammationneuronsnotebooksea-adseededsenescenceshowcasesingle-cellstatisticsstubtauwalkthrough

🌟 Spotlight Notebooks

Mitochondrial Dysfunction as a Driver of Neurodegeneration

How does mitochondrial dysfunction drive neurodegeneration across AD, PD, and ALS? Characterize PINK1/Parkin mitophagy pathway, mtDNA damage, ETC complex activity, and ROS generati

[]
Created: 2026-04-12
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Tau Pathology Propagation in Tauopathies — Mechanistic Dissection

How does misfolded tau spread through the brain in tauopathies? Characterize prion-like propagation mechanisms, cell-to-cell transfer, and the role of MAPT mutations, ApoE genotype

[]
Created: 2026-04-12
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SEA-AD Cell-Type Vulnerability Analysis

Comprehensive single-cell analysis of Alzheimer's disease using Seattle Alzheimer's Disease Brain Cell Atlas data. Includes gene expression heatmaps, differential expression analys

alzheimers single-cell sea-ad cell-types microglia
📊 SEA-AD Single-Cell Analysis: Cell-Type Vulnerability in Alzheimer's Disease
Created: 2026-04-04
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ACSL4-Driven Ferroptotic Priming in Disease-Associated Microglia

Hypothesis ID: h-seaad-v4-26ba859b | Composite Score: 0.82/1.00

SEA-AD gene-expression hypothesis-analysis microglia neurodegeneration
Created: 2026-04-04

Cell-Type Specific TREM2 Upregulation in DAM Microglia

Hypothesis ID: h-seaad-51323624 | Composite Score: 0.73/1.00

SEA-AD gene-expression hypothesis-analysis microglia neurodegeneration
Created: 2026-04-04

All Notebooks (55) (filtered by: seeded)

Does TFEB dysfunction cause neurodegeneration or represent a compensatory response to primary pathology?

The debate highlighted TFEB's role in mitochondrial-lysosomal coupling but couldn't resolve causation vs correlation. This distinction is critical for determining whether TFEB should be therapeuticall

seeded
Created: 2026-04-16
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APOE4 structural biology and therapeutic targeting strategies

**Analysis ID:** `sda-2026-04-01-gap-010` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Does reduced Prevotellaceae abundance cause PD pathology or result from it?

**Analysis ID:** `SDA-2026-04-11-gap-debate-20260410-111558-f9487fea` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Blood-brain barrier transport mechanisms for antibody therapeutics

**Analysis ID:** `sda-2026-04-01-gap-008` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Why do clinical manifestations overlap despite distinct underlying etiologies in immune-mediated myelopathies?

The abstract notes that clinical presentations overlap across different myelopathy etiologies, but the mechanistic basis for this convergent phenotype is not explained. Resolving this could improve di

seeded
Created: 2026-04-16
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Neuroinflammation and Microglial Priming in Early Alzheimer's Disease

> *Investigate mechanistic links between early microglial priming states, neuroinflammatory signaling, and downstream neurodegeneration in preclinical and prodromal AD.*

seeded
Created: 2026-04-16
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GBA-Synuclein Loop: Therapeutic Strategies for Parkinson's Disease

**Analysis ID:** `gba-pd` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Senolytic therapy for age-related neurodegeneration

**Analysis ID:** `sda-2026-04-01-gap-013` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Mechanistic role of APOE in neurodegeneration

**Analysis ID:** `sda-2026-04-01-gap-auto-fd6b1635d9` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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CRISPR-Based Therapeutic Approaches for Neurodegenerative Diseases

**Analysis ID:** `SDA-2026-04-03-gap-crispr-neurodegeneration-20260402` **Domain:** Neurodegeneration **Research Question:** Evaluate the potential of CRISPR/Cas9 and related gene-editing technologies

seeded
Created: 2026-04-16
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Autophagy-lysosome pathway convergence across neurodegenerative diseases

**Analysis ID:** `sda-2026-04-01-gap-011` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Aging Mouse Brain × SEA-AD: Cross-Species Comparative Analysis

What genes, pathways, and mechanisms are shared between age-dependent changes in the mouse brain and cell-type-specific vulnerabilities in human Alzheimer's disease? How does aging serve as a mechanis

seeded
Created: 2026-04-16
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Systemic immune profiling and peripheral immune contributions to neurodegeneration

How do peripheral immune system alterations influence CNS pathology and neurodegeneration in Alzheimer disease? Examine: (1) peripheral monocyte/macrophage trafficking across the blood-brain barrier,

seeded
Created: 2026-04-16
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Which cell types show the most significant expression changes for neurodegeneration genes in SEA-AD cohorts?

The debate mentioned gene expression profiling but did not specify which neural cell populations (neurons, microglia, astrocytes, oligodendrocytes) exhibit the most pronounced alterations. This cellul

seeded
Created: 2026-04-16
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TREM2 Therapeutic Strategy Post-INVOKE-2

**Analysis ID:** `sda-2026-04-01-001` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Senescent cell clearance as neurodegeneration therapy

**Analysis ID:** `SDA-2026-04-04-gap-senescent-clearance-neuro` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's disease pathogenesis through the gut-brain axis?

**Analysis ID:** `sda-2026-04-01-gap-20260401-225149` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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What neural circuits encode and maintain multi-generational migratory route memory?

The paper describes memory-based migration routes maintained across generations but doesn't explain the neural substrate for this long-term spatial memory storage and transmission. This represents a m

seeded
Created: 2026-04-16
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Immune atlas neuroinflammation analysis in neurodegeneration

Comprehensive analysis of immune cell subtypes in neurodegeneration: microglia subtypes (DAM, homeostatic, inflammatory), astrocyte reactivity states, T-cell infiltration. Anchor to existing TREM2 (h-

seeded
Created: 2026-04-16
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SEA-AD Cell-Type Vulnerability Analysis

**Analysis ID**: SDA-2026-04-03-gap-seaad-v4-20260402065846 **Quest**: Demo Showcase (Quest 16) — D16.2 **Date**: 2026-04-03 **Status**: Completed (4-round multi-agent debate)

seeded
Created: 2026-04-16
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Cell type vulnerability in Alzheimer's Disease (SEA-AD data)

**Analysis ID:** `SDA-2026-04-03-gap-seaad-20260402025452` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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RNA binding protein dysregulation across ALS FTD and AD

**Analysis ID:** `sda-2026-04-01-gap-v2-68d9c9c1` **Date:** 2026-04-02 **Domain:** neurodegeneration **Primary Cell Type:** Motor_Neurons **Hypotheses Generated:** 7 **Knowledge Graph Edges:** 20 ###

seeded
Created: 2026-04-16
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Neuroinflammation resolution mechanisms and pro-resolving mediators

**Analysis ID:** `sda-2026-04-01-gap-014` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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GBA-Synuclein Loop Therapeutics for PD

**Analysis ID:** `sda-2026-04-01-002` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Epigenetic clocks and biological aging in neurodegeneration

**Analysis ID:** `sda-2026-04-01-gap-v2-bc5f270e` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Gene Expression Changes in Aging Mouse Brain Predicting Neurodegenerative Vulnerability

> What gene expression changes in the aging mouse brain predict neurodegenerative vulnerability? > Use Allen Aging Mouse Brain Atlas data. Cross-reference with human AD datasets. > Produce hypotheses

seeded
Created: 2026-04-16
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Lipid metabolism dysregulation and membrane integrity in Alzheimer disease

**Analysis ID:** `SDA-2026-04-04-frontier-lipidomics-dcdbc360` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Cell type vulnerability in Alzheimer's Disease (SEA-AD data - v2)

What cell types are most vulnerable in Alzheimer's Disease based on SEA-AD transcriptomic data from the Allen Brain Cell Atlas? Identify mechanisms of cell-type-specific vulnerability in neurons, micr

seeded
Created: 2026-04-16
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Astrocyte reactivity subtypes in neurodegeneration

**Analysis ID:** `sda-2026-04-01-gap-007` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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4R-tau strain-specific spreading patterns in PSP vs CBD

**Analysis ID:** `sda-2026-04-01-gap-005` **Date:** 2026-04-02 **Domain:** neurodegeneration **Primary Cell Type:** Astrocytes **Hypotheses Generated:** 7 **Knowledge Graph Edges:** 20 ### Key Hypothe

seeded
Created: 2026-04-16
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Epigenetic reprogramming in aging neurons

Investigate mechanisms of epigenetic reprogramming in aging neurons, including DNA methylation changes, histone modification dynamics, chromatin remodeling, and partial reprogramming approaches (e.g.,

seeded
Created: 2026-04-16
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Can nanobodies achieve selective membrane penetration into tau-containing vesicles without affecting normal cellular vesicles?

The debate identified vesicle accessibility as a major concern for nanobody approaches but provided no evidence for selective membrane penetration. This technical barrier could invalidate the entire n

seeded
Created: 2026-04-16
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Sleep disruption as cause and consequence of neurodegeneration

**Analysis ID:** `sda-2026-04-01-gap-v2-18cf98ca` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Gut-Brain Axis Therapeutics for AD

**Analysis ID:** `sda-2026-04-01-003` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Which specific metabolic pathways in APOE4+ microglia are most therapeutically tractable?

While APOE4 disrupts microglial metabolism broadly, the debate didn't identify which specific disrupted pathways offer the best therapeutic targets. This prioritization is needed for focused drug deve

seeded
Created: 2026-04-16
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Neuroinflammation and microglial priming in early AD

**Analysis ID:** `SDA-2026-04-04-gap-neuroinflammation-microglial-20260404` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Circuit-level neural dynamics in neurodegeneration

**Analysis ID:** `SDA-2026-04-03-26abc5e5f9f2` **Domain:** neuroscience **Status:** completed

seeded
Created: 2026-04-16
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Synaptic pruning by microglia in early AD

**Analysis ID:** `sda-2026-04-01-gap-v2-691b42f1` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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What are the minimal structural requirements for HSP70/HSP90 inhibitors to achieve tau-selectivity over essential cellular functions?

The debate highlighted broad cellular toxicity of existing HSP inhibitors but did not resolve how to engineer selectivity for tau-associated chaperones. This structure-activity relationship gap preven

seeded
Created: 2026-04-16
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SEA-AD Single-Cell Analysis: Cell-Type Vulnerability in Alzheimer's Disease

What are the cell-type specific vulnerability mechanisms in Alzheimer's disease based on SEA-AD single-cell data?

seeded
Created: 2026-04-16
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Which specific post-translational modifications on pathological tau create druggable epitopes absent in physiological tau?

The debate mentioned tau PTM targeting but did not identify which modifications are both disease-specific and accessible for therapeutic intervention. This knowledge gap limits the development of PTM-

seeded
Created: 2026-04-16
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Quantitative proteomics of the aging synapse in early Alzheimer disease

What are the critical protein expression changes and post-translational modifications (phosphorylation, ubiquitination, glycosylation) at the aging synapse that drive early Alzheimer disease pathophys

seeded
Created: 2026-04-16
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Tau propagation mechanisms and therapeutic interception points

**Analysis ID:** `SDA-2026-04-04-gap-tau-prop-20260402003221` **Date:** 2026-04-02 **Domain:** neurodegeneration **Primary Cell Type:** Microglia **Hypotheses Generated:** 7 **Knowledge Graph Edges:**

seeded
Created: 2026-04-16
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TDP-43 phase separation therapeutics for ALS-FTD

**Analysis ID:** `sda-2026-04-01-gap-006` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Protein aggregation cross-seeding across neurodegenerative diseases

**Analysis ID:** `sda-2026-04-01-gap-9137255b` **Date:** 2026-04-02 **Domain:** neurodegeneration **Primary Cell Type:** Neurons **Hypotheses Generated:** 7 **Knowledge Graph Edges:** 20 ### Key Hypot

seeded
Created: 2026-04-16
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Selective vulnerability of entorhinal cortex layer II neurons in AD

**Analysis ID:** `sda-2026-04-01-gap-004` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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What is the actual quantitative contribution of FcRn-mediated transcytosis to BBB antibody transport in humans?

The debate revealed conflicting estimates ranging from <5% to 20% for FcRn's role in BBB transport, with species differences unresolved. This fundamental uncertainty undermines rational design of FcRn

seeded
Created: 2026-04-16
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Mitochondrial transfer between neurons and glia

**Analysis ID:** `sda-2026-04-01-gap-20260401231108` **Date:** 2026-04-02 **Domain:** neurodegeneration **Primary Cell Type:** Astrocytes **Hypotheses Generated:** 7 **Knowledge Graph Edges:** 20 ###

seeded
Created: 2026-04-16
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Mitochondrial transfer between astrocytes and neurons

**Analysis ID:** `sda-2026-04-01-gap-v2-89432b95` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Human connectome alterations and network-level dysfunction in Alzheimer disease

How do structural and functional connectivity changes in the human brain connectome drive cognitive decline in Alzheimer disease? Investigate: (1) default mode network disruption and amyloid depositio

seeded
Created: 2026-04-16
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Gut-Brain Axis Therapeutics for Alzheimer's Disease

**Analysis ID:** `gut-brain-ad` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Do tau-containing vesicles exhibit unique surface glycosylation patterns that distinguish them from normal vesicles?

The debate proposed targeting vesicle surface glycans but acknowledged no published data demonstrates unique glycosylation patterns on tau-containing vesicles. This fundamental question must be resolv

seeded
Created: 2026-04-16
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Digital biomarkers and AI-driven early detection of neurodegeneration

**Analysis ID:** `sda-2026-04-01-gap-012` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Perivascular spaces and glymphatic clearance failure in AD

**Analysis ID:** `sda-2026-04-01-gap-v2-ee5a5023` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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Microglia-astrocyte crosstalk amplification loops in neurodegeneration

**Analysis ID:** `sda-2026-04-01-gap-009` **Domain:** neurodegeneration **Status:** completed

seeded
Created: 2026-04-16
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