ID: h-fde8ac75360e
Hypothesis
A tau PTM barcode gates trans-synaptic templating
Specific combinations of tau phosphorylation, acetylation, and truncation mark assemblies that evade degradation and template after synaptic transfer.
EvidenceStrong (63%)📖 7 cit🗣 1 debates✓ 7 support✗ 2 oppose
✓ All Quality Gates Passed
🧪 Overview
Specific combinations of tau phosphorylation, acetylation, and truncation mark assemblies that evade degradation and template after synaptic transfer. Altering the PTM barcode should convert seed-competent tau into transferable but weakly pathogenic tau.
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD A["MAPT tau protein"] -->|"phosphorylation, acetylation, truncation"| B["Combined PTM barcode"] C["CDK5, GSK3B kinases"] -->|"hyperphosphorylation"| A D["p300, CREBBP acetyltransferases"] -->|"acetylation"| A E["Caspases, Calpains"] -->|"truncation"| A B -->|"specific PTM pattern"| F["Seed-competent tau assemblies"] F -->|"resistant to clearance"| G["Evasion of proteostasis"] G -->|"enhanced stability"| F F -->|"packaged in vesicles"| H["Exosome release"] H -->|"intercellular transport"| I["Trans-synaptic transfer"] I -->|"propagation of misfolding"| J["Templating of native tau"] J -->|"spreading of pathology"| K["Neurodegeneration"] K -->|"neuronal loss"| L["Cognitive decline"] M["PTM barcode modification"] -.->|"restores degradability"| G M -.->|"reduces seed competency"| F N["Kinase inhibitors"] -->|"target upstream PTMs"| M O["Deacetylase activation"] -->|"alters acetylation marks"| M
⚖️ Evidence
⚖️ Evidence Matrix5 supports1 contradicts
Supports
Interactions between Microtubule-Associated Protein Tau (MAPT) and Small Molecules.
Supports
Tau-targeting antisense oligonucleotide MAPT(Rx) in mild Alzheimer's disease: a phase 1b, randomized, placebo-controlled trial.
Supports
Tau filaments with the Alzheimer fold in human MAPT mutants V337M and R406W.
Supports
Isoform-specific patterns of tau burden and neuronal degeneration in MAPT-associated frontotemporal lobar degeneration.
Contradicts
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — MAPT
🧠 GTEx v10 Brain ExpressionJSON
Median TPM across 13 brain regions for MAPT from GTEx v10.
💉 Clinical Trials (5)Relevance: 82%
0
Active
Active
0
Completed
Completed
0
Total Enrolled
Total Enrolled
PHASE1
Highest Phase
Highest Phase
COMPLETED·NCT06584656 · Universidad de Granada
Healthy Aging Cognitive Function 1, Social Cerebrovascular Circulation
Aerobic exercise condition Resistance exercise condition
Safety Study of AADvac1, a Tau Peptide-KLH-Conjugate Active Vaccine to Treat Alzheimer's DiseasePHASE1
COMPLETED·NCT01850238 · Axon Neuroscience SE
Alzheimer Disease
AADvac1 Placebo
RECRUITING·NCT04906863 · Columbia University
Dementia, Early Onset
Blood draw Neurocognitive testing Medical questionnaire
COMPLETED·NCT04413344 · Kyoto University
Familial Alzheimer Disease (FAD) PSEN1 Mutation
Bromocriptine Mesilate Placebos
COMPLETED·NCT03978052 · Parc de Salut Mar
Alzheimer Disease Cognitive Decline
EGCG Placebo EGCG Healthy lifestyle recommendations
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for MAPT.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
↔
Stable
7d Momentum
▼ 1.8%
Volatility
Low
0.0036
Events (7d)
5
Price History
▼25.1%💾 Resource Usage
No resource usage or linked notebooks recorded for this hypothesis yet.
▸Metadatasource: v1_phase_c_backfill · origin_type: gap_debate
| source | v1_phase_c_backfill |
| origin_type | gap_debate |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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