{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T15:37:07Z","timestamp":1764085027909,"version":"3.45.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tau-based blood biomarkers are increasingly recognised as important for the diagnosis of Alzheimer\u2019s disease (AD). More than 60 proteolytic cleavage sites of tau have been identified, and current assays may miss critical information from some of the smaller protein fragments. By capturing a broader range of tau species, a polyclonal approach may offer greater interrogation of this complex \u201ctauosome\u201d and deliver valuable insights into the onset or progression of AD. A sheep was hyper-immunised with 2N4R tau113-251 peptide, encompassing the proline-rich region. An affinity-purified proline region polyclonal antibody (P.pAb) was derived from sheep serum, after four rounds of immunisation. Following characterisation of P.pAb, utility as a plasma biomarker\/diagnostic agent for AD was assessed using a single molecular array (Simoa) assay in a selected cohort consisting of clinically diagnosed AD patients and age-matched cognitively unimpaired (CU) individuals. Two assays were considered for this assessment including pairing the P.pAb with itself (P.pAb-P.pAb) to capture and detect multiple tau fragments in plasma, and pairing pTau217 capture mAb with P.pAb (pTau217-P.pAb). The P.pAb showed high affinity towards full-length tau and 113\u2013251 peptide immunogen and bound smaller 13-amino acid (aa) fragments throughout the proline rich region. The selected patient cohort was initially assessed by commercial neurofilament light (NfL) and pTau217 assays, the results of which were consistent with AD-related neurodegeneration in the AD sample and not in the CU group. The P.pAb-P.pAb and the pTau217-P.pAb assays were each able to distinguish between CU and AD groups; values were greater in AD (1.4-fold,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001 and 2.8-fold,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001, respectively). By contrast, a commercial total-tau (T-tau) assay did not distinguish between the two groups. We demonstrate the feasibility of an immunodiagnostic approach based on the detection of tau species containing the proline-rich region. The development of an affinity-purified proline region-specific pAb, capable of detecting multiple tau species in plasma, provides the foundation for a novel approach with potential applications in AD diagnosis and monitoring of disease progression.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-25864-x","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T15:29:14Z","timestamp":1764084554000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantification of plasma tau species containing the proline-rich region as a biomarker in Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"15","author":[{"given":"Mohammad","family":"Arastoo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lewis K.","family":"Penny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Lofthouse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Hitchcock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Moelders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sona","family":"Szalma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Porter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumya","family":"Palliyil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles R.","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claude M.","family":"Wischik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"25864_CR1","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.3233\/JAD-170727","volume":"62","author":"CM Wischik","year":"2018","unstructured":"Wischik, C. 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The clinical study protocol and associated documentation were approved by the ethics committee\/independent review board of each participating country: Health Research Authority (HRA) \/ NRES Committee West Midlands \u2013 Coventry & Warwickshire (Nottingham, UK) and Quorum Review IRB\u2014North American (U.S. & Canadian) Board (Seattle, WA, USA). All participants provided written informed consent prior to being enrolled in the study; if applicable, legal representatives provided consent on behalf of patients with reduced decision-making capacity. Subject consent for use of their biological samples for this research is covered by TRx-GTD-025 study- and country-specific informed consent forms. Only samples for which consent was obtained and not withdrawn, have been used in this research.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"41881"}}