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\":\"Semantic Variant Primary Progressive Aphasia: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Semantic Variant Primary Progressive Aphasia (condition). Clinician-written summaries and actionable practice insights. 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cut-off scores should be applied with caution in more diverse clinical populations.","value_numeric":null},{"paper_doi":"10.1177/10731911261457141","tag_type":"warning","value":"Study design is best classified as a prospective diagnostic validation cohort; it is not a randomized trial, so level of evidence is approximate.","value_numeric":null},{"paper_doi":"10.1177/10731911261457141","tag_type":"warning","value":"The paper was originally posted as a preprint in December 2024 and published in the journal Assessment in July 2026; findings are now peer-reviewed but the preprint version is what was provided.","value_numeric":null},{"paper_doi":"10.1177/10731911261457141","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously — the DART is freely available and fills a real gap, but external replication in non-WEIRD and non-English-speaking populations is still needed.","value_numeric":null}],"summaries":{"what_studied":"The Dynamic Affect Recognition Test (DART) — a free, 12-item video-based emotion identification tool — was validated in 257 early-stage persons with dementia (PWD; CDR ≤1, MMSE ≥20) across 8 neurodegenerative syndromes and 115 healthy controls, with concurrent MRI voxel-based morphometry (VBM) to confirm neuroanatomic correlates.","key_result":"All PWD groups scored worse than older healthy controls (p<0.001) except CBS. sbvFTD had the lowest mean score (5.3±2.1). A cut-off of ≤9/12 distinguished social cognition disorder syndromes (bvFTD, svPPA, sbvFTD) from controls with 93% sensitivity/67% specificity (AUC=87%); a cut-off of ≤7/12 distinguished sbvFTD from controls with 100% sensitivity/93% specificity (AUC=97%). Poorer DART scores correlated with right-predominant atrophy in the insula, temporal pole, caudate head, and superior frontal gyrus (pFWE<0.05).","limitations":"- Sample was predominantly White/WEIRD (89.3% European ancestry), limiting generalizability of normative cut-offs to diverse populations.\n- Some syndrome subgroups were small (e.g., lvPPA n=12, sbvFTD n=23), reducing precision of subgroup-level cut-offs.\n- No genetic or pathological diagnosis confirmation in most cases; DART cannot reliably differentiate individual dementia subtypes from one another beyond the groups studied.","practice_takeaway":"Clinicians evaluating early-stage dementia can use the freely available DART (via UCSF TabCAT or Qualtrics) as a brief (~3–5 min) add-on to flag emotion reading deficits — a score ≤9/12 suggests a social cognition disorder syndrome (bvFTD, svPPA, or sbvFTD) with high sensitivity, and a score ≤7/12 is highly specific for sbvFTD. The test is particularly useful when static face-emotion tasks are insufficient or ecologically invalid for cognitively impaired patients."}},{"doi":"10.1002/alz.71272","pmid":"42084118","title":"Digital seed amplification assay for TDP‐43 aggregate quantification in CSF","journal_title":"Alzheimer's & Dementia","journal_issn":"1552-5260","published_at":"2026-05-05T00:00:00.000Z","url":"https://doi.org/10.1101/2025.10.14.25338017","source_score":66,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-10","doi":"10.1002/alz.71272","days":"14","issn":"1552-5260","rank":"4","field":"Clinical Medicine","score":"66","category":"Clinical Neurology","categories":["Clinical Neurology"],"_categories":["Clinical Neurology"]},"pubmed":{"doi":"10.1002/alz.71272","title":"Digital seed amplification assay for TDP-43 aggregate quantification in CSF.","journal":"Alzheimer's & dementia : the journal of the Alzheimer's Association","methods":"","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.","abstract":"$30","keywords":["cerebrospinal fluid","frontotemporal lobar dementia","seed amplification assay","transactive response deoxyribonucleic acid binding protein 43"],"pubmed_id":"42084118","conclusions":"","publication_date":"2026-05-05T00:00:00"},"crossref":{"DOI":"10.1002/alz.71272","URL":"https://doi.org/10.1002/alz.71272","ISSN":["1552-5260","1552-5279"],"link":[{"URL":"https://alz-journals.onlinelibrary.wiley.com/doi/pdf/10.1002/alz.71272","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://alz-journals.onlinelibrary.wiley.com/doi/full-xml/10.1002/alz.71272","content-type":"application/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://alz-journals.onlinelibrary.wiley.com/doi/pdf/10.1002/alz.71272","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":"5","score":1,"title":["Digital seed amplification assay for TDP‐43 aggregate quantification in CSF"],"author":[{"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"}]},{"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"}]},{"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"}]},{"given":"Lily A. 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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":2,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Semantic Variant Primary Progressive Aphasia"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Semantic Variant Primary Progressive Aphasia"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Semantic Variant Primary Progressive Aphasia"}}}]]

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