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Although dementia subtypes have distinct mechanisms, overlapping symptoms make diagnosis without biomarkers difficult. Misdiagnosis has previously hindered drug development by enrolling patients non\u2010specifically in trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We developed a digital seed amplification assay (dSAA) that isolates individual aggregates in nanoliter compartments, enabling precise quantification of transactive response deoxyribonucleic acid binding protein 43 (TDP\u201043) seeds in cerebrospinal fluid (CSF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Testing 40 CSF samples from patients with genetic and sporadic frontotemporal lobar dementia with TDP (FTLD\u2010TDP), as well as healthy controls, we found elevated seed concentrations in FTLD\u2010TDP patients that correlated with disease severity, demonstrating the potential of dSAA as a sensitive diagnostic tool.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This study demonstrates a new quantitative, high\u2010sensitivity digital assay for TDP\u201043 seeds in CSF. The platform's single\u2010aggregate resolution and low limits of detection and quantification establish a technical foundation for developing a diagnostic and monitoring tool for FTLD\u2010TDP and other TDP\u201043\u2013related diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71272","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:00:20Z","timestamp":1777978820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Digital seed amplification assay for TDP\u201043 aggregate quantification in CSF"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7154-6225","authenticated-orcid":false,"given":"Ella","family":"Borberg","sequence":"first","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering at Harvard University  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Swank","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering at Harvard University  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Gilboa","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering at Harvard University  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily A. Wickland","family":"Shearer","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases Department of Neurology Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arek V.","family":"Melkonian","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering at Harvard University  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin C.","family":"Rolando","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering at Harvard University  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Walt","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital  Boston Massachusetts USA"},{"name":"Wyss Institute for Biologically Inspired Engineering at Harvard University  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8589-6891","authenticated-orcid":false,"given":"Andrew M.","family":"Stern","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases Department of Neurology Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts 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