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Current clinical criteria cannot reliably distinguish these subtypes, which have different underlying molecular mechanisms, genetic risk factors, and potentially ","entities":{"genes":["FTLD"],"diseases":["Alzheimer's Disease"]},"model_system":"human","_schema_version":1,"experiment_type":"clinical","primary_outcome":"Validate FTLD-Tau vs FTLD-TDP In Vivo Biomarker Differentiation","methodology_notes":"**Phase 1: Patient Recruitment and Clinical Characterization (Months 1-6)**\n\nRecruit 150 participants: 50 FTLD-Tau patients, 50 FTLD-TDP patients, and 50 age-matched healthy controls. Inclusion criteria include clinical diagnosis of FTLD based on consensus criteria, age 45-85 years, and availability of genetic testing results. Exclusion criteria include significant psychiatric comorbidities, recent immunosuppressive therapy, or contraindications to lumbar puncture or PET imaging. Conduct comprehensive neuropsychological assessment using Frontotemporal Lobar Degeneration-Clinical Dementia Rating (FTLD-CDR), Neuropsychiatric Inventory (NPI), and Frontal Behavioral Inventory (FBI).\n\n**Phase 2: Multimodal Biomarker Collection (Months 3-12)**\n\nCollect CSF via lumbar puncture for tau species analysis using ultrasensitive immunoassays (Simoa platform). Measure 4R-tau, 3R-tau, phospho-tau181, phospho-tau217, and TDP-43 levels. Perform [18F]MK-6240 tau-PET and [18F]AV-1451 imaging with quantita","replication_status":"single_study","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.897490","needs_review":true,"extraction_notes":"Backfilled from wiki source (no PMID 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wiki/therapeutics-mitochondrial-dynamics-modulators"},{"source_artifact_id":"wiki-therapeutics-social-engagement-cognitive-reserve","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 4x in wiki/therapeutics-social-engagement-cognitive-reserve"},{"source_artifact_id":"wiki-therapeutics-targeted-protein-stabilization-therapy","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/therapeutics-targeted-protein-stabilization-therapy"},{"source_artifact_id":"wiki-therapeutics-cbs-psp-clinical-trials-guide","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/therapeutics-cbs-psp-clinical-trials-guide"},{"source_artifact_id":"wiki-therapeutics-atn-biomarker-guided-ad-therapy","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/therapeutics-atn-biomarker-guided-ad-therapy"},{"source_artifact_id":"wiki-clinical-trials-pi-2620-tau-pet-phase-3-ftld-atypical-ad-nct05456503","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 21x in wiki/clinical-trials-pi-2620-tau-pet-phase-3-ftld-atypical-ad-nct05456503"},{"source_artifact_id":"wiki-clinical-trials-investigating-neurodegenerative-disorders-nct03225144","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 43x in wiki/clinical-trials-investigating-neurodegenerative-disorders-nct03225144"},{"source_artifact_id":"wiki-clinical-trials-nih-ctsa-psp-biospecimen-nct05067192","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 5x in wiki/clinical-trials-nih-ctsa-psp-biospecimen-nct05067192"},{"source_artifact_id":"wiki-clinical-trials-upenn-neurodegenerative-disease-repository-nct04715399","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/clinical-trials-upenn-neurodegenerative-disease-repository-nct04715399"},{"source_artifact_id":"wiki-clinical-trials-nct07115238-xtr006-tau-pet","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/clinical-trials-nct07115238-xtr006-tau-pet"},{"source_artifact_id":"wiki-clinical-trials-diagnosing-ftld-nct02964637","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 33x in wiki/clinical-trials-diagnosing-ftld-nct02964637"},{"source_artifact_id":"wiki-clinical-trials-progressive-supranuclear-palsy","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/clinical-trials-progressive-supranuclear-palsy"},{"source_artifact_id":"wiki-hypotheses-hyp_885074","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/hypotheses-hyp_885074"},{"source_artifact_id":"wiki-hypotheses-hyp_332160","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 6x in wiki/hypotheses-hyp_332160"},{"source_artifact_id":"wiki-datasets-proteome-atlas-neurodegenerative-diseases","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 16x in wiki/datasets-proteome-atlas-neurodegenerative-diseases"},{"source_artifact_id":"wiki-datasets-ftd-rankings","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 5x in wiki/datasets-ftd-rankings"},{"source_artifact_id":"wiki-cell-types-orbitofrontal-cortical-neurons-neurod","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 3x in wiki/cell-types-orbitofrontal-cortical-neurons-neurod"},{"source_artifact_id":"wiki-cell-types-prefrontal-cortex-layer-5-pyramidal","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/cell-types-prefrontal-cortex-layer-5-pyramidal"},{"source_artifact_id":"wiki-cell-types-cortical-pyramidal-layer5","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 3x in wiki/cell-types-cortical-pyramidal-layer5"},{"source_artifact_id":"wiki-cell-types-layer-6-corticothalamic-neurons","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/cell-types-layer-6-corticothalamic-neurons"},{"source_artifact_id":"wiki-cell-types-corticobasal-syndrome-neurons","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 3x in wiki/cell-types-corticobasal-syndrome-neurons"},{"source_artifact_id":"wiki-cell-types-frontotemporal-lobar-degeneration-neurons","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 44x in wiki/cell-types-frontotemporal-lobar-degeneration-neurons"},{"source_artifact_id":"wiki-cell-types-cortical-neurons-cbd","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/cell-types-cortical-neurons-cbd"},{"source_artifact_id":"wiki-cell-types-tauopathy-neurons","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/cell-types-tauopathy-neurons"},{"source_artifact_id":"wiki-mechanisms-ftd-tdp43-pathway","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 10x in wiki/mechanisms-ftd-tdp43-pathway"},{"source_artifact_id":"wiki-mechanisms-cbs-metal-dyshomeostasis","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 3x in wiki/mechanisms-cbs-metal-dyshomeostasis"},{"source_artifact_id":"wiki-mechanisms-ftd-fus-pathway","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/mechanisms-ftd-fus-pathway"},{"source_artifact_id":"wiki-mechanisms-ppa-logopenic-mechanisms","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 3x in wiki/mechanisms-ppa-logopenic-mechanisms"},{"source_artifact_id":"wiki-mechanisms-tauopathies","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 4x in wiki/mechanisms-tauopathies"},{"source_artifact_id":"wiki-mechanisms-frontotemporal-dementia-pathway","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 21x in wiki/mechanisms-frontotemporal-dementia-pathway"},{"source_artifact_id":"wiki-mechanisms-proteome-atlas-neurodegenerative-diseases","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 16x in wiki/mechanisms-proteome-atlas-neurodegenerative-diseases"},{"source_artifact_id":"wiki-mechanisms-nonfluent-agrammatic-ppa-mechanisms","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 9x in wiki/mechanisms-nonfluent-agrammatic-ppa-mechanisms"},{"source_artifact_id":"wiki-mechanisms-neuroinflammation-comparison","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 16x in wiki/mechanisms-neuroinflammation-comparison"},{"source_artifact_id":"wiki-mechanisms-tau-pathology-ad","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/mechanisms-tau-pathology-ad"},{"source_artifact_id":"wiki-mechanisms-psp-disease-progression-staging","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/mechanisms-psp-disease-progression-staging"},{"source_artifact_id":"wiki-mechanisms-chmp2b-escrit-iii-pathway","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/mechanisms-chmp2b-escrit-iii-pathway"},{"source_artifact_id":"wiki-mechanisms-semantic-variant-ftd-mechanisms","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD 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wiki/mechanisms-microglia-ftd-progression"},{"source_artifact_id":"wiki-mechanisms-cbs-calcium-dysregulation","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/mechanisms-cbs-calcium-dysregulation"},{"source_artifact_id":"wiki-mechanisms-ftd-cure-roadmap","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 25x in wiki/mechanisms-ftd-cure-roadmap"},{"source_artifact_id":"wiki-mechanisms-behavioral-variant-ftd-mechanisms","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 7x in wiki/mechanisms-behavioral-variant-ftd-mechanisms"},{"source_artifact_id":"wiki-mechanisms-progranulin-haploinsufficiency-ftd","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 4x in wiki/mechanisms-progranulin-haploinsufficiency-ftd"},{"source_artifact_id":"wiki-mechanisms-grn-progranulin-ftd-causal-chain","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/mechanisms-grn-progranulin-ftd-causal-chain"},{"source_artifact_id":"wiki-mechanisms-ggt-clinical-comparison","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/mechanisms-ggt-clinical-comparison"},{"source_artifact_id":"wiki-mechanisms-ad-ftd-tau-tdp-overlap-comparison","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 20x in wiki/mechanisms-ad-ftd-tau-tdp-overlap-comparison"},{"source_artifact_id":"wiki-mechanisms-4r-tauopathy-genetic-comparison","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 6x in wiki/mechanisms-4r-tauopathy-genetic-comparison"},{"source_artifact_id":"wiki-mechanisms-ggt-neuropathology","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/mechanisms-ggt-neuropathology"},{"source_artifact_id":"wiki-mechanisms-cbs-ftd-overlap","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 7x in wiki/mechanisms-cbs-ftd-overlap"},{"source_artifact_id":"wiki-mechanisms-ftd-tau-subtypes-comparison","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 14x in wiki/mechanisms-ftd-tau-subtypes-comparison"},{"source_artifact_id":"wiki-mechanisms-sleep-disruption-neurodegeneration","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 4x in wiki/mechanisms-sleep-disruption-neurodegeneration"},{"source_artifact_id":"wiki-resources-ad-brain-banks-tissue-repositories","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 3x in wiki/resources-ad-brain-banks-tissue-repositories"},{"source_artifact_id":"wiki-biomarkers-ftld-tau-tdp-distinction","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 58x in wiki/biomarkers-ftld-tau-tdp-distinction"},{"source_artifact_id":"wiki-biomarkers-amyloid-beta-42-40-ratio","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/biomarkers-amyloid-beta-42-40-ratio"},{"source_artifact_id":"wiki-biomarkers-cbs-liquid-biopsy-diagnostics","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 5x in wiki/biomarkers-cbs-liquid-biopsy-diagnostics"},{"source_artifact_id":"wiki-biomarkers-vilip-ykl-alzheimers","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/biomarkers-vilip-ykl-alzheimers"},{"source_artifact_id":"wiki-biomarkers-asl-perfusion-alzheimers","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/biomarkers-asl-perfusion-alzheimers"},{"source_artifact_id":"wiki-biomarkers-overview","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/biomarkers-overview"},{"source_artifact_id":"wiki-entities-al001","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 3x in wiki/entities-al001"},{"source_artifact_id":"wiki-gaps-tau-vs-tdp-43-fate-switching-ftd","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/gaps-tau-vs-tdp-43-fate-switching-ftd"},{"source_artifact_id":"wiki-brain-regions-claustrum","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/brain-regions-claustrum"},{"source_artifact_id":"wiki-brain-regions-prefrontal-cortex","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 4x in wiki/brain-regions-prefrontal-cortex"},{"source_artifact_id":"wiki-brain-regions-temporal-lobe","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 3x in wiki/brain-regions-temporal-lobe"},{"source_artifact_id":"wiki-diagnostics-cbs-liquid-biopsy-diagnostics","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 5x in wiki/diagnostics-cbs-liquid-biopsy-diagnostics"},{"source_artifact_id":"wiki-diagnostics-neuropathological-examination","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 10x in wiki/diagnostics-neuropathological-examination"},{"source_artifact_id":"wiki-diagnostics-bs-case-reports-clinical-series","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/diagnostics-bs-case-reports-clinical-series"},{"source_artifact_id":"wiki-experiments-progranulin-replacement-therapy-ftd","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 3x in wiki/experiments-progranulin-replacement-therapy-ftd"},{"source_artifact_id":"wiki-experiments-ftd-microglia-role-protective-destructive","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 7x in wiki/experiments-ftd-microglia-role-protective-destructive"},{"source_artifact_id":"wiki-diseases-late","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 7x in wiki/diseases-late"},{"source_artifact_id":"wiki-diseases-globular-glial-tauopathy","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 4x in wiki/diseases-globular-glial-tauopathy"},{"source_artifact_id":"wiki-diseases-logopenic-progressive-aphasia","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/diseases-logopenic-progressive-aphasia"},{"source_artifact_id":"wiki-diseases-primary-progressive-apraxia-of-speech","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/diseases-primary-progressive-apraxia-of-speech"},{"source_artifact_id":"wiki-diseases-tmem106b-ftd-modifiers","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 3x in wiki/diseases-tmem106b-ftd-modifiers"},{"source_artifact_id":"wiki-diseases-behavioral-variant-ftd","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 17x in wiki/diseases-behavioral-variant-ftd"},{"source_artifact_id":"wiki-diseases-frontotemporal-lobar-degeneration","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 102x in wiki/diseases-frontotemporal-lobar-degeneration"},{"source_artifact_id":"wiki-diseases-vcp-multisystem-proteinopathy","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/diseases-vcp-multisystem-proteinopathy"},{"source_artifact_id":"wiki-diseases-tauopathies-comparison","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 10x in wiki/diseases-tauopathies-comparison"},{"source_artifact_id":"wiki-diseases-semantic-variant-primary-progressive-aphasia","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 7x in wiki/diseases-semantic-variant-primary-progressive-aphasia"},{"source_artifact_id":"wiki-diseases-corticobasal-syndrome","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/diseases-corticobasal-syndrome"},{"source_artifact_id":"wiki-diseases-ftd","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 16x in wiki/diseases-ftd"},{"source_artifact_id":"wiki-diseases-primary-progressive-aphasia","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 9x in wiki/diseases-primary-progressive-aphasia"},{"source_artifact_id":"wiki-diseases-atypical-parkinsonism","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/diseases-atypical-parkinsonism"},{"source_artifact_id":"wiki-diseases-als-ftd-parkinsonism-comparison","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in wiki/diseases-als-ftd-parkinsonism-comparison"},{"source_artifact_id":"wiki-diseases-semantic-dementia","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 4x in wiki/diseases-semantic-dementia"},{"source_artifact_id":"wiki-diseases-tauopathy-comparison","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 23x in wiki/diseases-tauopathy-comparison"},{"source_artifact_id":"wiki-diseases-ftd-subtype-comparison","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 19x in wiki/diseases-ftd-subtype-comparison"},{"source_artifact_id":"wiki-diseases-cbs-clinical-phenotypes","link_type":"mentions","strength":0.5,"evidence":"Content: FTLD mentioned 6x in wiki/diseases-cbs-clinical-phenotypes"},{"source_artifact_id":"wiki-diseases-logopenic-variant-ppa","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: FTLD mentioned 2x in 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