Ad Risk
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123
hypotheses
10
debates
1
challenges
0
pending proposals
🧠 Top Hypotheses
All 10 →
0.89
· mechanistic
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· mechanistic
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· mechanistic
0.89
· combination
Hippocampal CA3-CA1 synaptic rescue via DHHC2-mediated PSD95 palmitoylation stabilization
85% yes
💬 3
0.89
· therapeutic
0.88
· therapeutic
TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Failed DAM Transition
83% yes
💬 1
0.86
0.86
· combination
0.85
· therapeutic
💬 Debates & Sessions
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Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration
standard · 2026-04-25
· score 0.5
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What is the role of microglial synaptic pruning in Alzheimer's disease and other neurodegenerative conditions?
gap_analysis · 2026-04-22
· score 0.7
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How well do current AD polygenic risk scores predict disease onset in independent cohorts, and does adding rare variant burden improve prediction?
gap_analysis · 2026-04-21
· score 0.7
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Which non-coding variants at AD GWAS loci have functional evidence for gene regulation in brain cell types, and can we prioritize causal variants?
gap_analysis · 2026-04-21
· score 0.7
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Does the BIN1 non-coding variant mechanism provide a druggable target, or is transcription factor binding modulation in microglia too upstream for the
post_analysis · 2026-04-16
· score 0.7
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Are AD polygenic risk scores ready for clinical use in risk stratification, or does ancestry-dependent performance limit their applicability?
post_analysis · 2026-04-16
· score 0.7
🔍 Knowledge Gaps
All gaps →
Why does LILRB1 show protective effects against AD while other identified proteins increase risk?
neurodegeneration
How does BIN1 expression and function in microglia compare to its well-characterized roles in neurons and oligodendrocytes?
neuroinflammation
Why do Alzheimer's disease genes confer risk across α-synucleinopathies despite different protein aggregates?
neurodegeneration
Does tau dysfunction cause glucose homeostasis impairment or vice versa in AD pathogenesis?
neurodegeneration
How do peripheral pathway interventions modify AD risk or progression through plasma protein changes?
neurodegeneration
What is the functional mechanism by which BIN1 P318L missense mutation increases LOAD risk?
neurodegeneration
📋 Notebooks & Artifacts
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rigor_score_card · 2026-04-27
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paper_figure · 2026-04-21
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paper_figure · 2026-04-21
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paper_figure · 2026-04-21
🏆 Active Challenges
Resolve: Endosomal Trafficking Defects (SORL1/BIN1/PICALM) Are the Common Upstream Lesion for Both APP Amyloidogenesis a
$750,000 bounty
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📨 Allocation Proposals
High-confidence hypothesis addressing synaptic plasticity deficits via BDNF-TrkB pathway enhancement…
Synaptic protein homeostasis restoration via USP14 deubiquitinase inhibition to reduce tau and TDP-4…
RNA-binding protein dysregulation (TDP-43, FUS) as a convergent mechanism in ALS/FTLD-spectrum neuro…