Protein Aggregation and Prion-like Spread Consensus

Consensus Summary

Misfolded amyloid, tau, alpha-synuclein, TDP-43, FUS, or other aggregate-prone proteins seed toxicity and propagate between vulnerable circuits.

This consensus cluster currently contains 110 active SciDEX hypotheses with average composite score 0.5702. Disease coverage: cross_neurodegeneration: 85, PD: 4, protein biochemistry: 4, AD: 3, ALS: 3, protein folding: 3, multi: 2, unspecified: 2.

Cross-Disease Signal

Shared disease buckets represented here: AD, PD, ALS, FTD, cross_neurodegeneration. Clusters with AD/PD/ALS/FTD co-coverage are priority targets for transfer hypotheses, debate scheduling, and Forge validation tasks.

Top Hypotheses

• SNCA conformer propagation across PD, DLB, and MSA (h-cross-synth-snca-synucleinopathy): multi, score 0.82

• MAPT tau seeding and release across AD, FTD, and PD-spectrum disease (h-cross-synth-mapt-tau-seeding): multi, score 0.812

• TIA1 Low-Complexity Domain Oxidation Drives Aberrant Stress Granule Assembly and TDP-43 Mislocalization in ALS Motor Neurons (h-alsmnd-54f981ca6a25): ALS, score 0.81

Category Definition

Mechanism terms used for deterministic assignment: amyloid, abeta, a-beta, tau, mapt, synuclein, snca, tdp-43, tdp43, fus, prion, aggregate, misfold, seeding, phase separation, condensate.

Provenance

Generated by scripts/atlas_mechanism_consensus_map.py for Atlas task be26e8ca-f0cf-4a8d-b2ed-31a8e19e8c71 from the live PostgreSQL hypotheses table. Hypotheses are linked to the cluster node through knowledge_edges.relation='belongs_to_pathway_cluster'.