📖

Mechanistic Proposal: Amyloid Plaque and Neurofibrillary Tangle Deposition is Essential for Accurate Modeling of AD in Mouse Models

wiki page Created: 2026-04-02 13:40:08 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-hypotheses-hyp_871297

Related Entities

Metadata

slug	hypotheses-hyp_871297
entity_type	hypothesis
kg_node_id	None

🌍 Provenance Graph 1 nodes, 0 edges

No provenance edges found

Linked Artifacts (378)

mentions🧪Context-Dependent CRISPR Activation in Specific Neuronal Sub90%

mentions🧪Purinergic Signaling Polarization Control70%

mentions🧪Lipid Droplet Dynamics as Phenotype Switches70%

mentions🧪Mechanosensitive Ion Channel Reprogramming70%

mentions🧫Microtubule domain analysis in adult axons50%

mentions🧫Tau depletion effects on neuronal development in primary cul50%

mentions🧫Pre-Symptomatic Tau Detection in MAPT Mutation Carriers50%

mentions🧪TREM2 Conformational Stabilizers for Synaptic Discrimination50%

mentions🧪TREM2-mediated microglial tau clearance enhancement50%

mentions🧪Selective APOE4 Degradation via Proteolysis Targeting Chimer50%

mentions🧪APOE Isoform Conversion Therapy50%

mentions🧪APOE4 Allosteric Rescue via Small Molecule Chaperones50%

mentions🧪Interfacial Lipid Mimetics to Disrupt Domain Interaction50%

mentions🧪Targeted APOE4-to-APOE3 Base Editing Therapy50%

mentions🧪APOE4-Selective Lipid Nanoemulsion Therapy50%

mentions🧪Competitive APOE4 Domain Stabilization Peptides50%

mentions🧪APOE Isoform Expression Across Glial Subtypes50%

mentions🧪TREM2-Dependent Microglial Senescence Transition50%

mentions🧪Cell-Type Specific TREM2 Upregulation in DAM Microglia50%

see_also📖Clinical Phenotypes and Subtypes of Corticobasal Syndrome50%

see_also📖FTLD-TDP Subtypes and Mechanisms50%

see_also📖AAIC 2026: Tau-PET Imaging and Fluid Biomarker Integration45%

see_also📖Alpha-Synuclein PET Imaging and Biomarker Advances45%

see_also📖Alpha-Synuclein Seeding Assays (RT-QuIC and PMCA)45%

see_also📖Imaging Biomarkers for Corticobasal Syndrome and Progressive45%

see_also📖Cell-Free DNA Biomarkers in Neurodegeneration45%

see_also📖Exosomal Biomarkers in Neurodegeneration45%

see_also📖Exosomal miR-155 in Neurodegeneration45%

see_also📖IL-6 (Interleukin-6) in Neurodegeneration45%

see_also📖Liquid Biopsy in Neurodegeneration45%

see_also📖Metabolomic Biomarkers in Neurodegeneration45%

see_also📖Multi-Analyte Biomarker Panel for Parkinson's Disease D45%

see_also📖Neuroimaging Biomarkers for Neurodegeneration45%

see_also📖NPTX1 and NPTXR CSF Markers Predict Alzheimer's Disease45%

see_also📖Polygenic Risk Score Integration Panel for Alzheimer's 45%

see_also📖CSF and Blood Biomarkers in Progressive Supranuclear Palsy45%

see_also📖p-Tau Biomarker in Immunoglobulin Light Chain and Transthyre45%

see_also📖Speech and Cognitive Biomarkers for Alzheimer's Disease45%

see_also📖Synaptic Biomarkers in Neurodegeneration45%

see_also📖VILIP-1 and YKL-40 - Alzheimer's Disease Biomarkers45%

see_also📖BEACoN Study - Biomarker Exploration in Aging, Cognition and45%

see_also📖BLAAC PD - Black and African Americans Connections to PD (NC45%

see_also📖Clostridium Butyricum for Motor and Non-motor Symptoms in Pa45%

see_also📖CNversyt and Megan Rodden ALS Trials45%

see_also📖Cognitive and Speech Rehabilitation in CBS (NCT05823421)45%

see_also📖Digital Therapeutic Platform for Swallowing and Drooling Pro45%

see_also📖First-in-Human 4R Tau Ligand Study in PSP (NCT07348276)45%

see_also📖Gait Analysis Parameter and Upper Limb Evaluation in Neurolo45%

see_also📖Gait and Upper Limb Evaluation in PSP (NCT07136844)45%

see_also📖GBA Brain Molecular Imaging and Blood Biomarkers for Precisi45%

see_also📖Utilisation of Health Services and Quality of Life in Atypic45%

see_also📖Phase 3 Study to Compare the Efficacy and Safety of Masitini45%

see_also📖Safety and Clinical Outcomes Study: Amniotic and Umbilical C45%

see_also📖A Phase IIB, Randomized, Double-Blind, Placebo-Controlled, M45%

see_also📖A Phase III, Randomized, Double-Blind, Placebo-Controlled, M45%

see_also📖A Multicenter, Phase III, Randomized, Double Blind, Placebo-45%

see_also📖A Phase 2b, Multicenter, Randomized, Double-Blind, Placebo-C45%

see_also📖Synaptic Therapy Alzheimer's Research Trial (START): A 45%

see_also📖Long-term Effects of Hearing Intervention on Brain Health in45%

see_also📖A Phase 2 Double-Blind, Randomized, Placebo-Controlled Trial45%

see_also📖A 6-month & 18-month Prospective, Randomized, Placebo-co45%

see_also📖A Phase 3, Randomized, Double-blind, Placebo-controlled, Par45%

see_also📖A Phase 3, Randomised, Double-blinded, Placebo-controlled St45%

see_also📖Olfactory Mucosa, Blood and Urine for Identification of Earl45%

see_also📖PCDH19-Related Epilepsy (EFMR) — Preclinical Gene Therapy Pr45%

see_also📖Whole-Body Photobiomodulation for Motor and Cognitive Change45%

see_also📖PI-2620 Tau PET Phase 3 (NCT05456503) - FTLD and Atypical AD45%

see_also📖Quality of Life and Caregiver Burden in PSP (NCT03638505)45%

see_also📖Rotigotine and Rivastigmine Combination Therapy for Alzheime45%

see_also📖Silymarin for Neuroprotection and Symptom Management in Park45%

see_also📖Social Behaviors and Quality of Life in Parkinson's Dis45%

see_also📖Swedish BioFINDER 2 Study: Biomarkers and Neurodegeneration 45%

see_also📖Clinical Efficacy and Mechanism of tDCS for Dysphagia in Par45%

see_also📖alexander-disease45%

see_also📖Alexander Disease Genetic Variants45%

see_also📖Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pi45%

see_also📖ATP13A9 and Parkinson's Disease45%

see_also📖Beta-Propeller Protein-Associated Neurodegeneration (BPAN)45%

see_also📖Callosal Disconnection and Interhemispheric Dysfunction in C45%

see_also📖Cross-National Cancer-Dementia Correlation and Shared Diseas45%

see_also📖Cancer-Dementia Inverse Correlation: Epidemiological Evidenc45%

see_also📖CARASIL (Cerebral Autosomal Recessive Arteriopathy with Subc45%

see_also📖Caregiver Burden and Support in Corticobasal Syndrome45%

see_also📖Caregiver Support and Palliative Care in Atypical [Parkinson45%

see_also📖Natural History and Prognosis of Corticobasal Syndrome45%

see_also📖China Neurodegeneration Epidemiology45%

see_also📖DALY Methodology — Neurodegeneration45%

see_also📖Disease Progression & Staging in Neurodegeneration45%

see_also📖Dysphagia and Nutritional Management in Corticobasal Syndrom45%

see_also📖Economic Burden — Neurodegeneration45%

see_also📖Environmental Toxins and Parkinson's Risk45%

see_also📖European Neurodegeneration Epidemiology45%

see_also📖Familial vs Sporadic Neurodegeneration Comparison45%

see_also📖Global Neurodegeneration Epidemiology45%

see_also📖HIV-Associated Neurocognitive Disorders (HAND)45%

see_also📖Hemiballismus and Hemichorea in Corticobasal Syndrome45%

see_also📖Hereditary Sensory and Autonomic Neuropathy (HSAN)45%

see_also📖India Neurodegeneration Epidemiology45%

see_also📖Investment Landscape: ALS45%

see_also📖Investment Landscape: Frontotemporal Dementia45%

see_also📖Investment Landscape: Huntington's Disease45%

see_also📖Investment Landscape: Parkinson's Disease45%

see_also📖Japan Neurodegeneration Epidemiology45%

see_also📖Japanese and German Case Series in Corticobasal Degeneration45%

see_also📖Jervell and Lange-Nielsen Syndrome45%

see_also📖LRRK2 Gene Variants and Mutations45%

see_also📖Manganese-Related Neurodegeneration (Manganism)45%

see_also📖MELAS Syndrome (Mitochondrial Encephalomyopathy, Lactic Acid45%

see_also📖Mirror Therapy and Sensory Re-education in Corticobasal Synd45%

see_also📖mitochondrial-dysfunction-neurodegeneration-comparison45%

see_also📖Mitochondrial Diseases and Neurodegeneration Comparison Matr45%

see_also📖Mitochondrial Membrane Protein-Associated Neurodegeneration 45%

see_also📖Neurodegeneration with Brain Iron Accumulation (NBIA)45%

see_also📖Potential Impact Measures — Neurodegeneration45%

see_also📖Nutritional Support and Dietary Interventions in Corticobasa45%

see_also📖Pantothenate Kinase-Associated Neurodegeneration (PKAN)45%

see_also📖Physical and Occupational Therapy in Corticobasal Syndrome45%

see_also📖Pantothenate Kinase-Associated Neurodegeneration (PKAN)45%

see_also📖PLA2G6-Associated Neurodegeneration (PLAN)45%

see_also📖Postural Dysfunction and Abnormalities in Corticobasal Syndr45%

see_also📖Pseudobulbar Affect and Emotional Lability in Corticobasal S45%

see_also📖Healthcare Economics and Cost of Illness in Progressive Supr45%

see_also📖PSP and Idiopathic Normal Pressure Hydrocephalus: Clinical O45%

see_also📖Quality of Life and Caregiver Burden in Progressive Supranuc45%

see_also📖Speech and Voice Disorders in PSP45%

see_also📖Sandhoff Disease45%

see_also📖Sialorrhea and Drooling in Corticobasal Syndrome45%

see_also📖Simultanagnosia and Balint's Syndrome in Corticobasal S45%

see_also📖Sleep Disorders in Neurodegeneration45%

see_also📖SNCA Gene Variants and Mutations45%

see_also📖Speech Therapy and Communication Aids in Corticobasal Syndro45%

see_also📖US Neurodegeneration Epidemiology45%

see_also📖Vocational Rehabilitation and Driving in Corticobasal Syndro45%

see_also📖Voice and Speech in Corticobasal Syndrome45%

see_also📖Extracellular Vesicle and Tunneling Nanotube-Mediated Spread45%

see_also📖ABCA7 Lipid Transport and Microglial Phagocytosis AD Causal 45%

see_also📖acetylcholine-signaling-neurodegeneration45%

see_also📖Shared Mechanisms Between Alzheimer and Parkinson Disease45%

see_also📖Advanced Glycation End Products in Neurodegeneration45%

see_also📖Advanced In Vitro Models for Neurodegeneration — Organoids, 45%

see_also📖ALS Biomarkers and Disease Monitoring45%

see_also📖Amylin Signaling in Neurodegeneration45%

see_also📖Antibody Therapy in Neurodegeneration45%

see_also📖Antisense Oligonucleotide (ASO) Therapy in Neurodegeneration45%

see_also📖APOE4 and Alzheimer's Disease Risk45%

see_also📖Autosis Pathway in Neurodegeneration45%

see_also📖Axon Guidance Pathways in Neurodegeneration45%

see_also📖Basal Ganglia Circuit Dysfunction in Neurodegeneration45%

see_also📖Blood-Brain Barrier and Neuroimmune Interface in CBS/PSP45%

see_also📖Blood-Brain Barrier Dysfunction and Therapeutic Delivery for45%

see_also📖becn1-autophagy-initiation-neurodegeneration-causal-chain45%

see_also📖Braak Staging and Tau Propagation Pathway45%

see_also📖C9orf72 Repeat Expansions in CBS and PSP45%

see_also📖CaMKII Signaling Pathway in Neurodegeneration45%

see_also📖Carbonic Anhydrase Modulator Therapy in Neurodegeneration45%

see_also📖Myoclonus and Cortical Hyperexcitability in Corticobasal Syn45%

see_also📖Multimodal Diagnostic Algorithm for CBS and PSP45%

see_also📖CBS/PSP Panxoneopathy and Membrane Biology45%

see_also📖VEGF and Angiogenesis Dysregulation in CBS/PSP45%

see_also📖Pupillometry and Chromatic Pupillometry in Corticobasal Synd45%

see_also📖Cerebral Amyloid Angiopathy in Neurodegeneration45%

see_also📖Cerebral Amyloid Angiopathy Pathway in Neurodegeneration45%

see_also📖Cholinergic System Dysfunction in Neurodegeneration45%

see_also📖Chrononutrition and Time-Restricted Eating in Neurodegenerat45%

see_also📖Neural Circuits in Neurodegeneration45%

see_also📖Cognitive Reserve and Resilience in Neurodegeneration45%

see_also📖Computational Disease Models for Neurodegeneration45%

see_also📖Convergent Pathways in Neurodegeneration45%

see_also📖Copper Homeostasis in Neurodegeneration45%

see_also📖COVID-19 Neurodegeneration Mechanism45%

see_also📖Diffusion MRI (DTI) in Neurodegeneration45%

see_also📖Digital Phenotyping in Neurodegeneration45%

see_also📖Down Syndrome Neurodegeneration Pathway45%

see_also📖Dystrophic Neurites in Neurodegeneration45%

see_also📖Endocannabinoid System in Neurodegeneration45%

see_also📖Endosomal-Lysosomal Pathway in Neurodegeneration45%

see_also📖Endosomal Sorting Defects in Neurodegeneration45%

see_also📖Endothelin Signaling Pathway in Neurodegeneration45%

see_also📖epigenetics-neurodegeneration45%

see_also📖ESCRT-III Inhibition by Alpha-Synuclein in Neurodegeneration45%

see_also📖FA2H-Associated Neurodegeneration Pathway45%

see_also📖FTDP-17 Clinical Phenotypes and Disease Progression45%

see_also📖Farnesoid X Receptor (FXR) Signaling in Neurodegeneration45%

see_also📖Galectin-3 Mechanism in Neurodegeneration45%

see_also📖Gangliosides in Neurodegeneration45%

see_also📖GBA Glucocerebrosidase Dysfunction and Parkinson's Dise45%

see_also📖GDF15/GDF11 Signaling in Neurodegeneration45%

see_also📖GDNF Signaling Pathway in Neurodegeneration45%

see_also📖Geniposide for Alzheimer's disease - immune biomarker t45%

see_also📖Ghrelin Signaling Pathway in Neurodegeneration45%

see_also📖Glial Tau Pathology in PSP and CBD45%

see_also📖Glucocorticoid Signaling Pathway in Neurodegeneration45%

see_also📖Glycosylation in Neurodegeneration45%

see_also📖Glymphatic Clearance Hypothesis — Impaired Aβ and Tau Remova45%

see_also📖Glymphatic and Vascular Clearance Dysfunction in 4R-Tauopath45%

see_also📖gp130/IL-6 Family Cytokine Signaling in Neurodegeneration45%

see_also📖Hippocampal Neurogenesis in Neurodegeneration45%

see_also📖Histone Modification Pathways in Neurodegeneration45%

see_also📖HMGB1 Signaling in Neurodegeneration45%

see_also📖Homocysteine Neurotoxicity and Neurodegeneration45%

see_also📖IGF-1 Signaling Pathway in Neurodegeneration45%

see_also📖IL-1 Signaling Pathway in Neurodegeneration45%

see_also📖Integrated Stress Response in Neurodegeneration45%

see_also📖interleukin-6-signaling-neurodegeneration45%

see_also📖Intrinsic Apoptosis Pathway in Neurodegeneration45%

see_also📖Ion Channel Dysfunction in Neurodegeneration: Cross-Disease 45%

see_also📖Iron and Neuromelanin Accumulation in PSP45%

see_also📖Kidney-Brain Neurodegeneration Axis45%

see_also📖Lipid Dysregulation in Neurodegeneration45%

see_also📖Lipid Metabolism Dysregulation in Neurodegeneration45%

see_also📖LRRK2 Kinase Activation and Endolysosomal Dysfunction in Par45%

see_also📖Lysosomal Calcium Dysregulation in Neurodegeneration45%

see_also📖Magnetic Resonance Spectroscopy in Neurodegeneration45%

see_also📖Metal Homeostasis Dysregulation in Neurodegeneration45%

see_also📖Metal Homeostasis in Neurodegeneration45%

see_also📖Microglial Priming Pathway in Neurodegeneration45%

see_also📖MicroRNA Dysfunction in Neurodegeneration45%

see_also📖Mineralocorticoid Receptor Signaling in Neurodegeneration45%

see_also📖Mitochondrial Dynamics Pathway in Neurodegeneration45%

see_also📖Mitochondrial Fusion in Neurodegeneration45%

see_also📖Molecular Chaperones in Neurodegeneration45%

see_also📖MSA Clinical Features and Diagnosis45%

see_also📖mTOR Signaling in Autophagy and Lysosomal Function45%

see_also📖mTOR Signaling in Neurodegeneration45%

see_also📖mTOR Signaling Pathway in Neurodegeneration45%

see_also📖Neural Circuit Disruption in Neurodegeneration45%

see_also📖Neurexin/Neuroligin Synaptic Adhesion Modulator Therapy in N45%

see_also📖Neurofilament Light Chain (NfL) Mechanism in Neurodegenerati45%

see_also📖Neuroinflammation in Parkinson's Disease Dementia and D45%

see_also📖Neuronal Hyperexcitability in Neurodegeneration45%

see_also📖Neuropil Threads in Neurodegeneration45%

see_also📖Neuroresilience Mechanisms and Evidence45%

see_also📖Neurotensin Signaling in Neurodegeneration45%

see_also📖Neurovascular Unit Dysfunction in Neurodegeneration45%

see_also📖NF-kB Signaling Pathway in Neurodegeneration45%

see_also📖Nitric Oxide Signaling in Neurodegeneration45%

see_also📖NLRP3 Inhibitors in Parkinson's Disease: Research and C45%

see_also📖Noradrenergic Signaling Pathway in Neurodegeneration45%

see_also📖Neuropeptide Y Signaling in Neurodegeneration45%

see_also📖NRF2 Signaling Pathway in Neurodegeneration45%

see_also📖Nuclear Pore Complex Dysfunction in Neurodegeneration45%

see_also📖Orexin Signaling in Neurodegeneration45%

see_also📖OSK Reprogramming and Yamanaka Factors in Neurodegeneration45%

see_also📖P-Body (Processing Body) Pathway in Neurodegeneration45%

see_also📖Paranodal Dysfunction in Neurodegeneration45%

see_also📖Paraptosis in Neurodegeneration45%

see_also📖Parthanatos in Neurodegeneration45%

see_also📖Pericyte Loss in Neurodegeneration45%

see_also📖Peripheral Immune-Brain Crosstalk in Neurodegeneration45%

see_also📖Pesticides and Parkinson Disease (Pest-PD) — NCT0642031045%

see_also📖PKR Pathway in Neurodegeneration45%

see_also📖PPAR Signaling Pathway in Neurodegeneration45%

see_also📖Prion Diseases in Neurodegeneration45%

see_also📖Prion-Like Spread in Neurodegeneration45%

see_also📖Prion Protein Metabolism in Neurodegeneration45%

see_also📖Progesterone Signaling Pathway in Neurodegeneration45%

see_also📖Prognostic Biomarkers in Neurodegeneration45%

see_also📖Protein Aggregation Comparison in Neurodegeneration45%

see_also📖Protein Aggregation Seeds in Neurodegeneration45%

see_also📖Protein O-GlcNAcylation Pathway in Neurodegeneration45%

see_also📖Advanced Proteolysis and Ubiquitin System Targeting in CBS/P45%

see_also📖Cortical Involvement and Neurodegeneration in Progressive Su45%

see_also📖Gait and Balance Disorders in Progressive Supranuclear Palsy45%

see_also📖HLA Haplotypes and Neuroinflammatory Profiles in PSP45%

see_also📖PSP Liquid-Liquid Phase Separation and Biomolecular Condensa45%

see_also📖PSP Lysosomal Dysfunction and Autophagy Impairment45%

see_also📖Metabolic Dysfunction and Insulin Resistance in Progressive 45%

see_also📖Pupillary and Visual Dysfunction in Progressive Supranuclear45%

see_also📖PSP Tau Propagation and Spreading Mechanisms45%

see_also📖PSP Weight Loss and Cachexia45%

see_also📖Purinergic Signaling in Neurodegeneration45%

see_also📖Quantum Biology and Coherent Energy Transfer in Neurodegener45%

see_also📖R-Loop Stress in Neurodegeneration45%

see_also📖RAN Translation in Neurodegeneration45%

see_also📖Retinal Degeneration Pathway in Neurodegeneration45%

see_also📖Ribosome Dysfunction in Neurodegeneration45%

see_also📖RNA Splicing in Neurodegeneration45%

see_also📖RNA-Targeted Therapies in Neurodegeneration45%

see_also📖Ribonuclease κ and Circular RNAs: A New Mechanism of Aging a45%

see_also📖S100 Protein Signaling Pathway in Neurodegeneration45%

see_also📖Senescent Cell Clearance in Neurodegeneration45%

see_also📖Serotonergic Dysfunction in Neurodegeneration45%

see_also📖Sex Differences in Neurodegeneration45%

see_also📖Short Chain Fatty Acids in Neurodegeneration45%

see_also📖Sigma-1 Receptor Signaling in Neurodegeneration45%

see_also📖Sirtuin-Mitochondrial Biogenesis Axis in Neurodegeneration45%

see_also📖Sleep Architecture Changes in CBS and PSP45%

see_also📖Sleep and Circadian Dysfunction in Alzheimer's Disease45%

see_also📖Sleep Dysfunction in Neurodegeneration45%

see_also📖Somatic Mutations and Brain Mosaicism45%

see_also📖Speech and Language Deficits in Corticobasal Syndrome45%

see_also📖SUMOylation in Neurodegeneration45%

see_also📖Synaptic Loss and Dysfunction Pathway45%

see_also📖synaptic-vesicle-cycling-neurodegeneration45%

see_also📖Synthetic Lethality and PARP Inhibition in Neurodegeneration45%

see_also📖Systemic Infection and Tau Pathology Acceleration45%

see_also📖T-Cell Dysfunction in Neurodegeneration45%

see_also📖Tau Seeding and Propagation Pathway45%

see_also📖TBK1 Autophagy and Neuroinflammation ALS/FTD Causal Chain45%

see_also📖Tertiary Lymphoid Organs in Neurodegeneration45%

see_also📖Therapeutic Targets in Neurodegeneration45%

see_also📖Transdiagnostic Proteomic Changes in Neurodegeneration45%

see_also📖ubiquitin-proteasome-dysfunction-neurodegeneration45%

see_also📖Ubiquitin-Proteasome System Dysfunction in Neurodegeneration45%

see_also📖Vagus Nerve Pathway in Neurodegeneration45%

see_also📖VEGF Signaling and Cerebral Angiogenesis in Neurodegeneratio45%

see_also📖vip-vasoactive-intestinal-peptide-signaling-neurodegeneratio45%

see_also📖WNK1-Bilirubin Signaling in Neuroinflammation and Neurodegen45%

see_also📖Wnt/β-Catenin Signaling Pathway in Neurodegeneration45%

see_also📖ALS Therapeutic Landscape — Programs by Phase and Modality45%

mentions🧫Mouse Cdk5, p35, and p39 mutations in neuronal migration44%

mentions🧫Microglial TREM2 Agonist In Vivo Efficacy44%

mentions🧫TREM2 Agonist Therapy for Parkinson's Disease — Experim44%

mentions🧫TREM2 Function in Alzheimer's Disease — From Risk Varia44%

mentions🔬Is disrupted sleep a cause or consequence of neurodegenerati40%

mentions🔬Anti-amyloid antibodies (lecanemab, donanemab) have ~0.1% br40%

mentions🔬APOE4 differs from APOE3 by C112R causing domain interaction40%

mentions🔬Comprehensive analysis of immune cell subtypes in neurodegen40%

mentions🔬What are the mechanisms underlying mechanistic role of apoe 40%

mentions🔬Investigate how lipid raft composition (cholesterol metaboli40%

mentions🔬What gene expression changes in the aging mouse brain predic40%