LATE (Limbic-Predominant Age-Related TDP-43 Encephalopathy)
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hypotheses
89
debates
58
challenges
0
pending proposals
🧠 Top Hypotheses
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· mechanistic
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💬 Debates & Sessions
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Structured research brief (iter2): ω-3 Docosahexaenoic Acid (DHA) Epoxide Generation via CYP2J2 to Protect Synaptic Membranes from Aβ-Induced Rigidifi
structured_research_brief · 2026-04-28
· score 0.6
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Which AD, PD, ALS, and FTD mechanisms recur across disease boundaries and yield falsifiable experiments?
gap_analysis · 2026-04-28
· score 0.7
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Structured research brief for hypothesis h-var-e95d2d1d86: Closed-loop optogenetic targeting PV interneurons to restore theta-gamma coupling and preve
gap_analysis · 2026-04-28
· score 0.7
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Structured research brief for hypothesis h-bdbd2120: Gamma entrainment therapy to restore hippocampal-cortical synchrony
gap_analysis · 2026-04-28
· score 0.9
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Is microglial priming (TREM2/CX3CR1/complement-C1q) genuinely causally upstream across Alzheimer's disease, Parkinson's disease, ALS, and multiple scl
gap_analysis · 2026-04-28
· score 0.6
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Extended debate: TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegeneration
hypothesis_debate · 2026-04-27
· score 0.9
🔍 Knowledge Gaps
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Can kinase inhibitors achieve therapeutic effects through off-target complement modulation?
pharmacology
Why do transferred mitochondria cause oxidative damage despite being metabolically active organelles?
neurodegeneration
What are the molecular mechanisms by which growth hormone activates periventricular neural stem cells?
neurodegeneration
What are the specific molecular mechanisms linking liver failure to neuropsychiatric symptoms in HE?
neurodegeneration
What molecular mechanisms regulate gastrosome formation and lipid processing within human microglia?
neuroinflammation
What molecular mechanisms link telomere dysfunction to inflammatory cytokine production in senescent endothelial cells?
cellular-senescence
📋 Notebooks & Artifacts
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🏆 Active Challenges
Senolytic Therapy for Age-Related Neurodegeneration: Target Cell Selectivity and CNS Delivery
$2,800,000 bounty
TREM2 Agonism vs Antagonism in Disease-Associated Microglia
$2,500,000 bounty
Solve: Senolytic therapy for age-related neurodegeneration
$962,784 bounty
Resolve: AD Biomarker Trajectory Is Subtype-Stratified, Not Universal — APOE/SORL1 vs NTRK1/BIN1
$750,000 bounty
Resolve: Post-Aβ Clearance Tau Autonomy Determines Efficacy of Anti-Tau Therapy After Amyloid Removal
$750,000 bounty
Resolve: TREM2-SIRT1 Metabolic Senescence Circuit as Microglial Rejuvenation Target
$500,000 bounty
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📨 Allocation Proposals
TREM2-dependent astrocyte-microglia cross-talk modulation to reduce neuroinflammation in AD. TREM2 R…
High-confidence hypothesis addressing synaptic plasticity deficits via BDNF-TrkB pathway enhancement…
Tau propagation blockade via extracellular tau seeding inhibitors. Strong preclinical evidence from …
APOE4-targeted lipid metabolism normalisation to reduce Aβ clearance deficiency. APOE4 is the strong…
Closed-loop transcranial focused ultrasound with 40 Hz gamma entrainment to restore hippocampal-cort…