2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T4b4,Dementia is commonly caused by underlying pathologies driven by misfolded protein aggregates. Although dementia subtypes have distinct mechanisms, overlapping symptoms make diagnosis without biomarkers difficult. Misdiagnosis has previously hindered drug development by enrolling patients non-specifically in trials. 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-43) seeds in cerebrospinal fluid (CSF). Testing 40 CSF samples from patients with genetic and sporadic frontotemporal lobar dementia with TDP (FTLD-TDP), as well as healthy controls, we found elevated seed concentrations in FTLD-TDP patients that correlated with disease severity, demonstrating the potential of dSAA as a sensitive diagnostic tool. This study demonstrates a new quantitative, high-sensitivity digital assay for TDP-43 seeds in CSF. The platform's single-aggregate resolution and low limits of detection and quantification establish a technical foundation for developing a diagnostic and monitoring tool for FTLD-TDP and other TDP-43-related diseases.31:T746,Abstract INTRODUCTION Dementia is commonly caused by underlying pathologies driven by misfolded protein aggregates. Although dementia subtypes have distinct mechanisms, overlapping symptoms make diagnosis without biomarkers difficult. Misdiagnosis has previously hindered drug development by enrolling patients non‐specifically in trials. METHODS 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‐43) seeds in cerebrospinal fluid (CSF). RESULTS Testing 40 CSF samples from patients with genetic and sporadic frontotemporal lobar dementia with TDP (FTLD‐TDP), as well as healthy controls, we found elevated seed concentrations in FTLD‐TDP patients that correlated with disease severity, demonstrating the potential of dSAA as a sensitive diagnostic tool. DISCUSSION This study demonstrates a new quantitative, high‐sensitivity digital assay for TDP‐43 seeds in CSF. The platform's single‐aggregate resolution and low limits of detection and quantification establish a technical foundation for developing a diagnostic and monitoring tool for FTLD‐TDP and other TDP‐43–related diseases. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"CSF Biomarker Assay: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on CSF Biomarker Assay (modality). 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CSF","updated":"2026-05-08T16:02:47+00:00","published_date":"2025-10-15","best_oa_location":{"url":"https://www.medrxiv.org/content/medrxiv/early/2025/10/15/2025.10.14.25338017.full.pdf","pmh_id":null,"url_for_pdf":"https://www.medrxiv.org/content/medrxiv/early/2025/10/15/2025.10.14.25338017.full.pdf","url_for_landing_page":"https://doi.org/10.1101/2025.10.14.25338017"}}},"created_at":"2026-05-12T13:18:09.756Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.1002/alz.71272","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"condition","value":"Frontotemporal Lobar Degeneration with TDP-43","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"condition","value":"Semantic Variant Primary Progressive Aphasia","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"generic","value":"TDP-43 seed amplification assay","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"modality","value":"CSF Biomarker Assay","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"sample_size","value":"n=40","value_numeric":40},{"paper_doi":"10.1002/alz.71272","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"study_design","value":"Diagnostic Accuracy Study","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"warning","value":"Specificity of 60% at the reported cutoff is modest; the assay is not validated for clinical decision-making.","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"warning","value":"Study design classification as 'Diagnostic Accuracy Study' is an approximation; the authors describe this as a proof-of-concept/technical development study with exploratory diagnostic analyses.","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"warning","value":"The study lacked a diseased non-TDP comparator group (e.g., FTLD-tau), so cross-seeding false positives cannot be excluded.","value_numeric":null},{"paper_doi":"10.1002/alz.71272","tag_type":"warning","value":"This paper was initially posted as a preprint (medRxiv, October 2025) and the published journal version is dated May 2026; peer-review status at time of preprint posting was unconfirmed — clinicians should verify final peer-reviewed publication.","value_numeric":null}],"summaries":{"what_studied":"A digital seed amplification assay (dSAA) was developed to quantify pathological TDP-43 aggregates in CSF. It was tested on 40 CSF samples: 10 GRN mutation carriers, 10 C9ORF72 repeat expansion carriers, 10 sporadic svPPA patients, and 10 age-matched healthy controls from the ALLFTD cohort.","key_result":"FTLD-TDP patients had significantly higher CSF TDP-43 seed concentrations than controls (p = 0.0334). At a cutoff of 0.528 nM, sensitivity was 87% and specificity was 60%. Seed concentrations correlated with disease severity (FTLDCDR; R² = 0.308, p = 0.0002). GRN carriers showed significantly elevated seeds vs. controls; C9ORF72 and svPPA groups showed numerically higher but not statistically significant elevations.","limitations":"Small sample (n=40) with limited statistical power and no validation cohort; most patients lacked autopsy-confirmed pathological classification; no FTLD-tau or other non-TDP disease control group, preventing assessment of cross-seeding specificity.","practice_takeaway":"This dSAA is not yet ready for clinical use but shows promise as a future CSF biomarker tool to identify FTLD-TDP patients and track disease severity. Clinicians enrolling patients in TDP-43-directed trials should watch for validated versions of this assay, which could improve patient selection."}}],"initialOffset":1,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"CSF Biomarker Assay"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"CSF Biomarker Assay"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"CSF Biomarker Assay"}}}]]

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