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All 8 Hypotheses 1 Papers 1 Wikis 1 Gaps 1 Colliders 1 Debates 1 Bounties 0 Missions 1 Work packets 1 Genes 0 Diseases 0 Phenotypes 0 Gene ontology 0

+ Hypotheses 1 + Papers 1 + Wikis 1 ✓ Gaps 1 + Colliders 1 + Debates 1 + Bounties 0 + Missions 1 + Work packets 1 + Genes 0 + Diseases 0 + Phenotypes 0 + Gene ontology 0

30 results

Gap Why do plasma p-tau217 and tau-PET show equivalent predictive performance despite measuring different aspects of tau pathology? rel 0.80

tau phosphorylation) and tau-PET (regional brain tau aggregation) have

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Gap Why does sTREM2 mediation vary substantially between P-tau (20-25%) and T-tau (36-44%) for BIN1 variants? rel 0.70

tau relationship compared to BIN1-P-tau, suggesting different pathways

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Gap Why does HMW tau induce stronger glial activation than fibrillar tau without causing neurodegeneration? rel 0.70

tau toxicity mechanisms. Gap type: unexplained_observation Source paper: Tau

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Gap What molecular mechanisms enable HMW tau to propagate more rapidly than fibrillar tau across neural networks? rel 0.70

tau propagation. Gap type: unexplained_observation Source paper: Tau seeding

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Gap How does endolysosomal tau seed escape specifically enhance cytoplasmic tau aggregation versus clearance? rel 0.60

tau seeds access cytoplasmic tau pools to promote aggregation, the competitive

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Gap Why does CDK5/p25 activation reduce tau phosphorylation when it's considered a major tau kinase? rel 0.60

tau kinase activation and phospho-tau accumulation to cortical and hippocampal

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Gap Why does plasma p-tau181 show stronger correlation with amyloid than tau pathology despite being a tau biomarker? rel 0.60

tau (ρ=0.25), which is counterintuitive for a tau-derived

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Gap What alternative pathways drive tau hyperphosphorylation if major tau kinases are not aberrantly activated? rel 0.60

tau kinase activation and phospho-tau accumulation to cortical and hippocampal

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Gap Can selective modulation of 14-3-3 protein isoforms differentially affect tau propagation versus normal tau function? rel 0.60

tau functions. Source: Debate session sess_SDA-2026-04-02-gap-tau

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Gap How does synaptic tau abundance reconcile with the established dogma of tau as primarily an axonal protein? rel 0.60

tau contradicts the long-held view of tau as predominantly

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Gap How does exogenous human 4R-tau coaptate endogenous monkey 3R-tau during transneuronal spread? rel 0.60

tau and monkey 3R-tau during spreading, but the molecular

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Gap Why do tau-targeting therapies fail clinically despite tau's stronger correlation with cognitive decline than Aβ? rel 0.60

tau levels correlate more strongly with cognitive impairment than Aβ depositions

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Gap Does FYN kinase directly regulate tau packaging into extracellular vesicles or only synaptic tau localization? rel 0.60

tau-prop-20260402003221 (Analysis: SDA-2026-04-02-gap-tau

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Gap What are the specific molecular mechanisms linking tau dysfunction to glucose homeostasis alterations? rel 0.50

tau impairments and glucose homeostasis remain unclear, despite evidence that

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Gap Which specific HSP90 co-chaperone interactions promote versus prevent tau pathogenesis and propagation? rel 0.50

tau propagation remain unresolved. Source: Debate session sess_SDA-2026-04-02-gap-tau

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Gap How does CMA dysfunction mechanistically enhance cell-to-cell propagation of pathogenic tau? rel 0.50

tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation

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Gap Why does acetylated tau preferentially utilize macroautophagy and endosomal microautophagy over CMA? rel 0.50

tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation

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Gap What mechanisms link conformationally changed tau and S202-phosphorylated tau to dendritic spine loss? rel 0.50

tau species coincide with reduced spine density and memory deficits

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Gap What molecular mechanism drives insulin-induced 4R-tau expression in developmentally immature neurons? rel 0.50

tau in embryonic neurons that normally only express 3R-tau

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Gap Why do positive CSF tau biomarker changes from anti-tau treatments fail to translate to cognitive benefits? rel 0.50

tau treatments consistently show small but significant reductions in CSF tau

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Gap What endosomal mechanisms mediate enhanced tau release from AD synapses upon depolarization? rel 0.50

tau peptides from AD synapses and demonstrate increased tau release

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Gap What are the specific molecular determinants that govern tau strain selection during prion-like propagation? rel 0.50

tau-propagation-20260402 (Analysis: SDA-2026-04-02-gap-tau

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Gap What accounts for the safety-efficacy profile differences between tau immunotherapy and other tau-targeting approaches? rel 0.50

tau immunotherapy as 'relatively safe and efficacious but narrow' compared

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Gap What molecular mechanisms link 4R tau isoform imbalance to delayed retinal cell differentiation? rel 0.50

tau-mutant models exhibit both 4R tau predominance and sustained

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Gap Why do AD and CTE tau prions fail to robustly infect single isoform-expressing cells despite containing both 3R and 4R tau? rel 0.50

tau isoforms cannot efficiently infect cells expressing only 3R or 4R tau

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Gap Why does plasma p217+tau fail to distinguish between Initial (A+T-) and Early (A+TMTL+) AD stages? rel 0.50

tau phosphorylation and regional brain tau accumulation. Understanding this discordance

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Gap Does metabolic dysfunction in neurodegenerative diseases drive pathological tau isoform switching? rel 0.50

tau isoforms raises the question of whether metabolic dysregulation contributes

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Gap Should tau-targeted therapies be redesigned to account for Aβ-tau synergy rather than targeting tau alone? rel 0.50

tau may need reconsideration given the synergistic relationship with Aβ. This

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Gap Can chaperone enhancement approaches overcome tau seed saturation effects in advanced pathology? rel 0.50

tau propagation rates are unknown. Source: Debate session sess_SDA-2026-04-04-gap-tau

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Gap What mechanisms explain how LC degeneration exacerbates tau pathology beyond increased tau burden? rel 0.50

tau pathology increases, indicating tau-independent mechanisms. Understanding these pathways

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