{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T02:16:48Z","timestamp":1793758608518,"version":"4.6.1"},"reference-count":86,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:sec id=\"ab-nrv260003-1\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Classifying disease based on underlying pathobiology rather than clinical phenotype has implications for the development of biomarkers and therapy development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-nrv260003-2\">\n                    <jats:title>Observations<\/jats:title>\n                    <jats:p>Transactive response DNA-binding protein 43 kDa (TDP-43) pathology is observed across a range of clinically defined neurodegenerative disorders including limbic predominant age-related encephalopathy (LATE), most cases of amyotrophic lateral sclerosis (ALS), inclusion body myositis, multisystem proteinopathy, and approximately half the cases of frontotemporal dementia (FTD). Despite this shared biology, the current nosology for these neurodegenerative disorders is based on their distinct clinical phenotypes. An alternative approach recognizes the central role of TDP-43 pathology in disease pathogenesis, reserving the use of clinical terms like ALS, FTD, or LATE to describe phenotypic manifestations of underlying pathobiology. This approach also recognizes the converging biomarker and neuropathological data indicating that pathology begins presymptomatically, before the overt clinical manifestations of disease appear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-nrv260003-3\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In proposing a pathobiological definition of disease, the goal is to provide a road map for developing biomarkers that accurately reflect the underlying pathobiology of disease and for advancing therapeutic candidates that effectively target fundamental disease mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaneurol.2026.2812","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:43:25Z","timestamp":1787586205000},"page":"1013","source":"Crossref","is-referenced-by-count":2,"title":["TDP-43\u2013Associated Neurodegenerative Disease 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