{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:40:00Z","timestamp":1792014000818,"version":"4.4.0"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PNRR\u2010MCNT2\u20102023\u201012377336"],"award-info":[{"award-number":["PNRR\u2010MCNT2\u20102023\u201012377336"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013278","name":"EU Joint Programme \u2013 Neurodegenerative Disease Research","doi-asserted-by":"publisher","award":["2021\u2010650\u2010104"],"award-info":[{"award-number":["2021\u2010650\u2010104"]}],"id":[{"id":"10.13039\/100013278","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Seed amplification assays (SAAs) have shown promising results in detecting misfolded transactive response (TAR) DNA\u2010binding protein 43 (TDP\u201043) in cerebrospinal fluid (CSF) of genetic frontotemporal dementia (FTD). To date, the use of SAA has yet to be evaluated in presymptomatic individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Thirty patients carrying\n                      <jats:italic>GRN<\/jats:italic>\n                      or\n                      <jats:italic>C9orf72<\/jats:italic>\n                      mutations, 2 microtubule\u2010associated protein tau (\n                      <jats:italic>MAPT<\/jats:italic>\n                      ) carriers, 14 presymptomatic subjects, and 27 controls underwent CSF collection. We used SAA for detecting misfolded TDP\u201043 (TDP\u201043_SAA) and single molecule array (SIMOA) technology for neurofilament light chain (NfL) dosage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      TDP\u201043 seeding activity was detected in 67% of TDP\u201043\u2010linked symptomatic patients, with a specificity of 93%. Almost half of presymptomatic subjects tested positive, mostly\n                      <jats:italic>GRN<\/jats:italic>\n                      carriers. Interestingly, among TDP\u201043_SAA positive presymptomatic individuals, two\n                      <jats:italic>GRN<\/jats:italic>\n                      carriers underwent phenoconversion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>TDP\u201043_SAA can also detect misfolded TDP\u201043 in the CSF of presymptomatic individuals. A possible link exists between positive TDP\u201043_SAA and conversion to the symptomatic phase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Seed amplification assay of transactive response (TAR) DNA\u2010binding protein 43 (TDP\u201043_SAA) can detect misfolded TDP\u201043 in the cerebrospinal fluid (CSF) of patients with genetic frontotemporal dementia (FTD), linked to\n                            <jats:italic>GRN<\/jats:italic>\n                            and\n                            <jats:italic>C9orf72<\/jats:italic>\n                            mutations.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>TDP\u201043_SAA can detect misfolded TDP\u201043 also in the CSF of presymptomatic individuals.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            In both groups, most TDP\u201043_SAA positive cases were carriers of\n                            <jats:italic>GRN<\/jats:italic>\n                            mutation.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Two\n                            <jats:italic>GRN<\/jats:italic>\n                            carriers that resulted TDP\u201043_SAA positive converted to the symptomatic phase of the disease.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70989","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T06:35:24Z","timestamp":1765866924000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Detection of TDP\u201043 seeds in CSF of presymptomatic and symptomatic genetic FTD\/ALS"],"prefix":"10.1002","volume":"21","author":[{"given":"Ilaria Linda","family":"Dellarole","sequence":"first","affiliation":[{"name":"SSD Laboratory Medicine\u2010Laboratory of Clinical Pathology Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Aprea","sequence":"additional","affiliation":[{"name":"Neurology 8 \u2013 Dementias and degenerative diseases of CNS Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan 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