Hypothesis corpus
Scored, debated, and tradable. Each hypothesis carries composite, novelty, impact, mechanistic, druggability, and safety scores — plus a live market price when a collider is open.
Showing neuroscience hypotheses, sorted by Composite score.
GluN2B-Mediated Thalamocortical Control of Glymphatic Tau Clearance
GRIN2B neuroscience 96%Thalamocortical circuit integrity differentiates normal aging from mild cognitive impairment, with decreased neural complexity and increased synchronization being hallmarks of dysfunction
h-var-e2b5a7e7dbCortico-Striatal Synchrony Restoration via NMDA Modulation
GRIN2B neuroscience 95%Thalamocortical circuit integrity differentiates normal aging from mild cognitive impairment, with decreased neural complexity and increased synchronization being hallmarks of dysfunction
h-var-5e33600319Microglial-Mediated Tau Clearance Dysfunction via TREM2 Receptor Impairment
MAPT neuroscience 94%Early electrophysiological disintegration of hippocampal neural networks occurs in a locus coeruleus tau-seeding mouse model of Alzheimer's disease, suggesting this pathway is critical for circuit mai…
h-var-59fc393ba6Glymphatic-Mediated Tau Clearance Dysfunction
MAPT neuroscience 86%Early electrophysiological disintegration of hippocampal neural networks occurs in a locus coeruleus tau-seeding mouse model of Alzheimer's disease, suggesting this pathway is critical for circuit mai…
h-var-95b0f9a6bcTREM2-Mediated Microglial Dysfunction Disrupts Perivascular Tau Clearance
TREM2 neuroscience 86%Early electrophysiological disintegration of hippocampal neural networks occurs in a locus coeruleus tau-seeding mouse model of Alzheimer's disease, suggesting this pathway is critical for circuit mai…
h-var-7c976d9fb7Microglial-Mediated Tau Clearance Dysfunction via TREM2 Signaling
TREM2 neuroscience 83%Early electrophysiological disintegration of hippocampal neural networks occurs in a locus coeruleus tau-seeding mouse model of Alzheimer's disease, suggesting this pathway is critical for circuit mai…
h-var-ce41f0efd7Inhibiting Heparan Sulfate Proteoglycan Receptor-Mediated Neuronal Tau Uptake
SULF1/SULF2 neuroscience 82%HSPGs mediate tau uptake via LRP1-dependent mechanism
h-c90cca1826Thalamocortical Feedforward Inhibition Imposes Rhythm on Glymphatic Waste Clearance Windows
GRIN2B (VB thalamocortical relay neurons); circuit-level target neuroscience 81%Slow-wave sleep augments glymphatic clearance 60%
h-9268cd08d2Dual-Circuit Tau Vulnerability Cascade
MAPT neuroscience 77%Early electrophysiological disintegration of hippocampal neural networks occurs in a locus coeruleus tau-seeding mouse model of Alzheimer's disease, suggesting this pathway is critical for circuit mai…
h-var-8412ce00a4Thalamocortical Synchrony Restoration via NMDA Modulation
GRIN2B neuroscience 77%Thalamocortical circuit integrity differentiates normal aging from mild cognitive impairment, with decreased neural complexity and increased synchronization being hallmarks of dysfunction
h-cd60e2ecEnhancing Microglial Phagocytosis of Extracellular Tau via TREM2 Activation
TREM2 neuroscience 77%TREM2 deficiency increases tau seeding and spreading in P301S mice
h-c58ac188fcSelective LXRβ agonists restore ABCA1/ABCG1 expression and APOE lipidation in APOE4 astrocytes, normalizing cholesterol export and reducing AD-relevant neurotoxicity
NR1H2 (LXRβ), ABCA1, ABCG1 neuroscience 76%LXR agonist improves APOE lipidation and reduces amyloid in mice
h-3f4cb83e0cGluN2B-CX3CL1 Axis Controls Microglial Tau Phagocytosis
GRIN2B → CX3CL1 → CX3CR1/TREM2 axis neuroscience 76%CX3CL1-CX3CR1 signaling modulates tau pathology
h-bcbc70473bCholinergic Basal Forebrain-Hippocampal Circuit Protection
MAPT neuroscience 76%Early electrophysiological disintegration of hippocampal neural networks occurs in a locus coeruleus tau-seeding mouse model of Alzheimer's disease, suggesting this pathway is critical for circuit mai…
h-var-f687d4593bAPOE4 astrocytes exhibit impaired cholesterol efflux via ABCA1/ABCG1 transporters, driving intracellular lipid droplet accumulation and secondary neuronal cholesterol deficiency
ABCA1, ABCG1 neuroscience 76%APOE4 astrocytes show increased lipid droplet accumulation and perturbed neutral lipid metabolism
h-bc8867b7adDopaminergic Ventral Tegmental-Hippocampal Circuit Protection
MAPT neuroscience 75%Early electrophysiological disintegration of hippocampal neural networks occurs in a locus coeruleus tau-seeding mouse model of Alzheimer's disease, suggesting this pathway is critical for circuit mai…
h-var-bc4357c8c5TDP-43 condensation thermodynamics as a therapeutic target and biomarker for nuclear-cytoplasmic compartmentalization
TARDBP (TDP-43 protein); IPO4/IP09 (nuclear import receptors as secondary targets) neuroscience 72%TDP-43 pathology present in >95% of ALS cases
h-6f6c9d3cGluN2B Tonic Activity Suppresses Glymphatic Perfusion Via Vasomotion Dysregulation
GRIN2B (thalamocortical projection neurons); downstream: NOS1, AQP4 neuroscience 70%Memantine enhances CSF tracer clearance in mice (mechanism reinterpreted)
h-19689f6ce7TREM2 R47H variant synergizes with APOE4 to collapse microglial lipid clearance capacity, causing extracellular lipid accumulation that feeds back to astrocyte lipid droplet formation
TREM2, APOE neuroscience 68%TREM2 deficiency causes lipid droplet accumulation in microglia
h-909199b568Cortical Layer 5 Pyramidal Neuron GluN2B-Mediated Hyperactivity Drives Tau Secretion Into Glymphatic Flow
GRIN2B (L5 pyramidal neurons); downstream: ADAM10/ADAM17 neuroscience 68%Activity-dependent tau release is NMDAR-dependent
h-a1edc6af93TFEB-mediated transcriptional upregulation of lysosomal genes as a therapeutic strategy for AD
TFEB (TFEC) neuroscience 68%TFEB overexpression in N2a cells reduces Aβ42 secretion
h-7ed7b242deMicroglial TREM2-Mediated Tau Phagocytosis Impairment
MAPT neuroscience 68%Early electrophysiological disintegration of hippocampal neural networks occurs in a locus coeruleus tau-seeding mouse model of Alzheimer's disease, suggesting this pathway is critical for circuit mai…
h-var-69c66a84b3Astrocytic-Mediated Tau Clearance Dysfunction via TREM2 Signaling
TREM2 neuroscience 67%Early electrophysiological disintegration of hippocampal neural networks occurs in a locus coeruleus tau-seeding mouse model of Alzheimer's disease, suggesting this pathway is critical for circuit mai…
h-var-c46786d2abLocus Coeruleus-Hippocampal Circuit Protection
MAPT neuroscience 67%Early electrophysiological disintegration of hippocampal neural networks occurs in a locus coeruleus tau-seeding mouse model of Alzheimer's disease, suggesting this pathway is critical for circuit mai…
h-23b94ed8