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Renard","orcid":null,"orcid_url":null,"slug":"bernhard-y-renard-86953755","url":"/science/scientists/bernhard-y-renard-86953755/"},{"id":"hs-scientist-bf99e337a710ffa4","name":"Michael DeTure","orcid":null,"orcid_url":null,"slug":"michael-deture-bf99e337","url":"/science/scientists/michael-deture-bf99e337/"},{"id":"hs-scientist-528a2aded0663d7a","name":"Ann C. McKee","orcid":null,"orcid_url":null,"slug":"ann-c-mckee-528a2ade","url":"/science/scientists/ann-c-mckee-528a2ade/"},{"id":"hs-scientist-0e6aa39126b472be","name":"Bradley T. Hyman","orcid":null,"orcid_url":null,"slug":"bradley-t-hyman-0e6aa391","url":"/science/scientists/bradley-t-hyman-0e6aa391/"},{"id":"hs-scientist-ba8f64d6c81b99a2","name":"Hanno Steen","orcid":null,"orcid_url":null,"slug":"hanno-steen-ba8f64d6","url":"/science/scientists/hanno-steen-ba8f64d6/"},{"id":"hs-scientist-805311b77ea34463","name":"Judith A. Steen","orcid":"0000-0002-8167-0772","orcid_url":"https://orcid.org/0000-0002-8167-0772","slug":"judith-a-steen-805311b7","url":"/science/scientists/judith-a-steen-805311b7/"}],"claims":[{"epistemic_status":"qualified","evidence_count":2,"importance":"central","qualification":"El AUC reportado agrega clasificadores y conjuntos de datos; el desempeño fue variable en enfermedades raras y la validación independiente se restringió a FLEXITau con 11 rasgos.","statement":"Los clasificadores random forest distinguieron cada tauopatía frente a grupos balanceados de otras tauopatías y controles, con AUC promedio alta en los tres tipos de datos.","type":"predictive"},{"epistemic_status":"supported","evidence_count":2,"importance":"central","qualification":"La separación se observó en tejido cerebral post mortem; no equivale a un biomarcador clínico validado en pacientes vivos.","statement":"Los perfiles de abundancia, modificaciones postraduccionales, cortes proteolíticos y extensión de modificación de tau difirieron entre grupos neuropatológicos y permitieron agruparlos parcialmente.","type":"descriptive"},{"epistemic_status":"uncertain","evidence_count":1,"importance":"supporting","qualification":"Es una interpretación mecanística de asociaciones en tejido post mortem, apoyada por literatura previa, no una prueba causal dentro de este diseño.","statement":"El artículo propone que el corte de tau y la neutralización de carga en el dominio de unión a microtúbulos podrían contribuir a estabilizar fibrillas.","type":"mechanistic"},{"epistemic_status":"supported","evidence_count":1,"importance":"supporting","qualification":"Son medianas por miligramo de tejido húmedo en una cohorte post mortem, no concentraciones de un fluido diagnóstico.","statement":"La mediana de tau patológica insoluble varió marcadamente entre grupos, con los valores más altos en fAD y AD y los más bajos en controles, DLB, PSP y PiD.","type":"descriptive"}],"curation":{"evidence_links":61,"grounded_claims":4,"note":"El paper aporta un atlas molecular de tauopatias en tejido post mortem y distingue patrones asociados con diferentes demencias. La ficha conserva como limites que no demuestra un biomarcador clinico listo y que la estabilizacion de fibrillas sigue siendo una inferencia mecanistica.","source_scope":"authorized_body"},"id":"hs-paper-1244803fd9185c9b","identifiers":{"doi":"10.1016/j.cell.2025.12.036","doi_url":"https://doi.org/10.1016/j.cell.2025.12.036"},"interpretation_cautions":[{"code":"clinical_translation_not_validated","description":"No presentar estos rasgos como biomarcadores clínicos listos: falta validación en muestras accesibles de pacientes vivos.","evidence_count":1,"severity":"caution"},{"code":"class_imbalance_generalizability","description":"El desempeño agregado puede ocultar inestabilidad en grupos raros y pequeños.","evidence_count":1,"severity":"caution"},{"code":"observational_mechanistic_inference","description":"Las propuestas sobre estabilización de fibrillas son hipótesis mecanísticas, no efectos causales probados por este diseño.","evidence_count":1,"severity":"info"}],"limitations":[{"evidence_count":2,"origin":"authors","statement":"No se dispuso de raza, etnia o ascendencia; la cohorte probablemente fue mayoritariamente caucásica y puede estar sesgada."},{"evidence_count":2,"origin":"hadox_analysis","statement":"La frecuencia de pacientes para PTM/cortes es presencia-ausencia dependiente de detectabilidad y abundancia, no estequiometría; no debe interpretarse como magnitud de modificación."},{"evidence_count":1,"origin":"authors","statement":"Los tamaños y el balance entre grupos limitan la generalización, especialmente para PSP y PiD."},{"evidence_count":1,"origin":"authors","statement":"Los rasgos provienen de tejido post mortem y necesitan validación en sangre o líquido cefalorraquídeo antes de considerarse biomarcadores clínicos."},{"evidence_count":2,"origin":"authors","statement":"No hubo mujeres en el grupo CTE por indisponibilidad de muestras, lo que puede afectar sus resultados."}],"media":{"conceptual_illustration":true,"disclosure":"ILUSTRACIÓN CONCEPTUAL · NO ES EVIDENCIA","gallery":[{"height":1402,"media_type":"image/png","position":1,"role":"cover_hero","sha256":"59cfb9b66c85f04761945f32469bd6361d2e3c1be63e3ba88b1e1da44d931eb9","url":"/science/media/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1/editorial/01.png","width":1122},{"height":1568,"media_type":"image/png","position":2,"role":"primary_finding","sha256":"88923d7e8aba911f7fe82ff754502db43fbf45328c87e303d620771bf62fdca4","url":"/science/media/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1/editorial/02.png","width":1003},{"height":1402,"media_type":"image/png","position":3,"role":"plain_language","sha256":"bf35ebd66f73cfb65451bfedf161e57e2de2a3227fae68b8dc4b0bdc2d885d59","url":"/science/media/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1/editorial/03.png","width":1122},{"height":1402,"media_type":"image/png","position":4,"role":"evidence_boundary","sha256":"d954ec1c36c2c9fbad901b3000efed0ab363f1c4ff7670f08972b8bcb2e2c8db","url":"/science/media/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1/editorial/04.png","width":1122}],"hero":{"height":1402,"media_type":"image/png","position":1,"role":"cover_hero","sha256":"59cfb9b66c85f04761945f32469bd6361d2e3c1be63e3ba88b1e1da44d931eb9","url":"/science/media/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1/editorial/01.png","width":1122},"illustration_is_evidence":false},"methods":[{"category":"computational_analysis","evidence_count":2,"statement":"Se compararon varios clasificadores; la selección de rasgos usó eliminación con random forest y validación cruzada repetida, seguida de evaluación fuera de bolsa, hold-back y cohorte independiente."},{"category":"design","evidence_count":1,"statement":"Diseño transversal comparativo de tejido cerebral post mortem con grupos definidos neuropatológicamente y una cohorte secundaria de validación."},{"category":"ethics","evidence_count":1,"statement":"Los tejidos se obtuvieron con consentimiento y aprobaciones institucionales de los biobancos."},{"category":"measurement","evidence_count":2,"statement":"Las fracciones de tau insoluble se analizaron por LC-MS/MS y FLEXITau dirigido; se midieron péptidos y relaciones light/heavy con revisión manual de transiciones."},{"category":"population_or_material","evidence_count":1,"statement":"La unidad material fue tejido cerebral de autopsia procedente de biobancos; los diagnósticos se confirmaron post mortem por neuropatología."},{"category":"sampling","evidence_count":1,"statement":"Las muestras provinieron de seis biobancos NIH en la primera cohorte y cinco repositorios en la segunda, con criterios explícitos de selección."},{"category":"statistical_analysis","evidence_count":2,"statement":"Las comparaciones usaron pruebas t bilaterales con corrección FDR y alfa 0.05; el agrupamiento jerárquico empleó distancia euclidiana y se evaluaron clasificadores con ROC/AUC."}],"publication":{"article_type":"research_article","date":"2026-02-01","journal":"Cell","language":"en","publisher":"Cell Press (Elsevier)","year":2026},"quantitative_findings":[{"comparison":"Cada tauopatía frente a mezcla balanceada de otras tauopatías y controles","estimate":"0.86 ± 0.13","estimate_numeric":0.86,"evidence_count":1,"interval_lower":null,"interval_type":"SD 0.13","interval_upper":null,"measure":"AUC promedio ± desviación estándar","outcome":"Discriminación promedio de random forest entre una tauopatía y no-self balanceado","p_value":null,"population":"Clasificadores sobre PTM, cortes y FLEXITau de la cohorte primaria","unit":"AUC"},{"comparison":"No aplica","estimate":"195 sitios de corte","estimate_numeric":195,"evidence_count":1,"interval_lower":null,"interval_type":null,"interval_upper":null,"measure":"Conteo","outcome":"Sitios de corte proteolítico mapeados en tau","p_value":null,"population":"Muestras combinadas del estudio","unit":"sitios"},{"comparison":"No aplica","estimate":"145 PTM","estimate_numeric":145,"evidence_count":1,"interval_lower":null,"interval_type":null,"interval_upper":null,"measure":"Conteo","outcome":"Sitios de modificación postraduccional mapeados en tau","p_value":null,"population":"Muestras combinadas del estudio","unit":"sitios"},{"comparison":"Ocho grupos neuropatológicos y controles","estimate":"fAD ∼3450; AD ∼1220; CTE ∼190; CBD ∼150; PSP ∼30; PiD ∼30; DLB ∼20; CTR ∼15 fmol/mg","estimate_numeric":null,"evidence_count":1,"interval_lower":null,"interval_type":null,"interval_upper":null,"measure":"Mediana por grupo","outcome":"Abundancia mediana de tau patológica insoluble por grupo","p_value":null,"population":"Cohorte primaria post mortem","unit":"fmol/mg de peso húmedo"}],"reporting":[{"dimension":"claim_evidence_alignment","evidence_count":2,"framework":"general_empirical","rationale":"Las afirmaciones descriptivas y clasificatorias se vinculan a resultados; las proyecciones clínicas y explicaciones mecanísticas exceden lo demostrado por tejido post mortem transversal.","status":"assessable"},{"dimension":"limitations_transparency","evidence_count":2,"framework":"strobe","rationale":"Hay una sección dedicada y además se reconocen restricciones de sexo y ascendencia; faltan implicaciones más explícitas del diseño transversal para causalidad.","status":"assessable"},{"dimension":"methods_transparency","evidence_count":2,"framework":"general_empirical","rationale":"El reporte describe procedencia y selección de muestras, preparación, instrumentación y procesamiento con detalle operativo; esto no demuestra ausencia de sesgo.","status":"assessable"},{"dimension":"reporting_completeness","evidence_count":2,"framework":"general_empirical","rationale":"El reporte identifica pregunta, cohortes, mediciones, análisis, resultados y limitaciones. La puntuación mide completitud del reporte, no validez científica.","status":"assessable"},{"dimension":"reproducibility_transparency","evidence_count":1,"framework":"top_2025","rationale":"Datos, código y archivos intermedios se declaran públicos y los métodos son detallados; no se verificó aquí la ejecución independiente de esos artefactos.","status":"assessable"},{"dimension":"statistical_transparency","evidence_count":2,"framework":"general_empirical","rationale":"Se reportan pruebas, FDR, alfa, validación cruzada y evaluación de clasificadores; el texto principal no presenta para cada comparación todos los intervalos y métricas desagregadas.","status":"assessable"}],"research_question":"¿Qué rasgos moleculares de tau patológica —abundancia, isoformas, modificaciones postraduccionales y sitios de corte— distinguen entre tauopatías y controles, y con qué capacidad clasificatoria?","schema_version":"hadox.public-science.v2","selection":{"abstract_only":false,"algorithmic_gate":"closed_insufficient_history","algorithmic_selection":false,"approved_on":"2026-07-22","decision":"approved","full_text_read":true,"route":"editorial_fulltext_review"},"slug":"molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1","social":{"caption":"ARTÍCULO DE REVISTA\n\nInvestigación de Mukesh Kumar y 30 coautores, publicada en Cell.\nHadox realizó la curaduría y divulgación; no realizó el estudio.\n\nSegún el análisis, la abundancia, las modificaciones y los cortes de tau formaron perfiles que separaron parcialmente varios grupos neuropatológicos.\n\nEl equipo analizó tau insoluble de 203 sujetos, validó parte del análisis en otros 142 y entrenó clasificadores con esos rasgos.\n\nLa tau patológica no mostró una única huella molecular en todas las enfermedades estudiadas.\n\nLos resultados sugieren que esas huellas ayudaron a distinguir grupos neuropatológicos, aunque el desempeño fue más variable en enfermedades raras.\n\nLímite: Los autores señalan una frontera clara: los datos proceden de cerebro post mortem; antes de hablar de biomarcadores clínicos, los rasgos deben validarse en sangre o líquido cefalorraquídeo.\n\nFuente científica:\nCell — Molecular features of human pathological tau distinguish tauopathy-associated dementias\nhttps://doi.org/10.1016/j.cell.2025.12.036\n\nExpediente Hadox Science:\nhttps://hadox.org/science/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1\n\n#HadoxScience #Ciencia","cards":[{"height":1350,"media_type":"image/png","position":1,"role":"cover","sha256":"eb767df3a22e1da50017a36ac8131dd97cc0baf6efb1f5f0e7c6999919a6219a","url":"/science/media/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1/social/01.png","width":1080},{"height":1350,"media_type":"image/png","position":2,"role":"finding","sha256":"26735ce1dcf7f2d766f5cb02912c50b4af1a47b15ce13e41e1bfecaa14d63daa","url":"/science/media/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1/social/02.png","width":1080},{"height":1350,"media_type":"image/png","position":3,"role":"plain_language","sha256":"ffd8f0bd739c41a29bfb1ece5e3e9a0035eded7a3d6d50f5ea7b91965302c379","url":"/science/media/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1/social/03.png","width":1080},{"height":1350,"media_type":"image/png","position":4,"role":"boundary","sha256":"32588c2a35a33fc96b7c619f7003604aeea003b55f46f9894e2cced7c06021ab","url":"/science/media/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1/social/04.png","width":1080}],"dossier_url":"https://hadox.org/science/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1","language":"es-MX","links_to_dossier":true,"publication_url":null,"status":"draft","trace_count":12},"study_design":{"family":"cross_sectional","label":"Estudio proteómico comparativo transversal en tejido cerebral post mortem con cohorte independiente de validación"},"summary":{"boundaries":["No demuestra diagnóstico en vida, utilidad clínica, causalidad de PTM o cortes sobre agregación, representatividad poblacional amplia ni desempeño estable para todas las tauopatías raras. Tampoco convierte por sí solo estos rasgos en PET ligands, terapias o biomarcadores listos."],"conclusions":["En tejido cerebral post mortem, el estudio construye un atlas amplio de química de tau y encuentra patrones de abundancia, PTM, cortes y modificación que separan parcialmente tauopatías. Random forest alcanzó AUC media de 0.86 ± 0.13 y FLEXITau fue probado en una cohorte independiente reducida. El aporte sólido es molecular y clasificatorio en tejido; su valor clínico y sus hipótesis mecanísticas permanecen por validar."]},"title":"Molecular features of human pathological tau distinguish tauopathy-associated dementias","topics":[{"level":"domain","name":"Health Sciences","slug":"domain-health-sciences","url":"/science/topics/domain-health-sciences/"},{"level":"field","name":"Medicine","slug":"field-medicine","url":"/science/topics/field-medicine/"},{"level":"subfield","name":"Physiology","slug":"subfield-physiology","url":"/science/topics/subfield-physiology/"},{"level":"topic","name":"Alzheimer's disease research and treatments","slug":"topic-alzheimer-s-disease-research-and-treatments","url":"/science/topics/topic-alzheimer-s-disease-research-and-treatments/"},{"level":"registry_discipline","name":"Biomedicine","slug":"registry-discipline-biomedicine","url":"/science/topics/registry-discipline-biomedicine/"},{"level":"registry_discipline","name":"Cell Biology","slug":"registry-discipline-cell-biology","url":"/science/topics/registry-discipline-cell-biology/"},{"level":"registry_discipline","name":"Molecular Biology","slug":"registry-discipline-molecular-biology","url":"/science/topics/registry-discipline-molecular-biology/"}],"transparency":[{"category":"code_availability","evidence_count":1,"statement":"Código y archivos intermedios se declararon públicos en Zenodo.","status":"reported"},{"category":"conflict","evidence_count":0,"statement":"El cuerpo completo extraído no contiene una declaración sustantiva de conflictos de interés.","status":"not_reported"},{"category":"data_availability","evidence_count":1,"statement":"Los datos de proteómica MS se declararon públicos en PRIDE con cuatro identificadores.","status":"reported"},{"category":"funding","evidence_count":1,"statement":"El artículo identifica financiamiento público y filantrópico por estudio, biobancos e infraestructura.","status":"reported"},{"category":"materials_availability","evidence_count":1,"statement":"No se generaron reactivos nuevos o únicos.","status":"not_applicable"},{"category":"registration","evidence_count":0,"statement":"No se reporta preregistro ni plan de análisis registrado.","status":"not_reported"}],"url":"/science/papers/molecular-features-of-human-pathological-tau-distinguish-tauopathy-associated-dementias-abae62b1/"}