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Elevated p-tau levels have also been associated with cerebral deposition of Danish amyloid and prion protein amyloid. Here we analyzed p-tau in serum from four different cohorts of people with the most common types of systemic amyloidosis, transthyretin (ATTR) amyloidosis and immunoglobulin light chain (AL) amyloidosis. We found higher levels of serum p-tau181 in the AL and ATTR groups than in controls. Subsequent analyses revealed that these effects were more pronounced in the presence of polyneuropathy (PNP) and in AL compared to ATTR amyloidosis. Individuals with different forms of PNP that were not due to amyloidosis did not exhibit elevated p-tau181 levels. In cases of presymptomatic (genetic) ATTR, p-tau181 levels increased as a function of predicted years from symptom onset. Additional measurement of p-tau217 in one cohort revealed similar increases, and discriminated people with AL and those with ATTR from controls equally as well as p-tau181. These findings suggest that elevated serum p-tau levels are not specific to Alzheimer disease and may also serve as a diagnostic tool of ATTR and AL amyloidosis, with potential utility in distinguishing amyloidosis-related PNP from PNP of other etiologies.<\/jats:p>","DOI":"10.1038\/s41591-026-04272-2","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:02:56Z","timestamp":1773223376000},"page":"1676-1681","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Blood phosphorylated tau elevation as a biomarker in immunoglobulin light chain and transthyretin amyloidosis"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4188-5111","authenticated-orcid":false,"given":"Stephan A.","family":"Kaeser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8460-4415","authenticated-orcid":false,"given":"Stephanie A.","family":"Schultz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"H\u00e4sler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3728-6519","authenticated-orcid":false,"given":"Ying","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Oberm\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-8596","authenticated-orcid":false,"given":"Kathrin","family":"Brockmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0375-4460","authenticated-orcid":false,"given":"Johan","family":"Bijzet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3974-6830","authenticated-orcid":false,"given":"Hans","family":"Nienhuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-1684","authenticated-orcid":false,"given":"Mario","family":"Nuvolone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Obici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5994-5138","authenticated-orcid":false,"given":"Giovanni","family":"Palladini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1917-6746","authenticated-orcid":false,"given":"Ute","family":"Hegenbart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4853-5579","authenticated-orcid":false,"given":"Stefan O.","family":"Sch\u00f6nland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9045-1072","authenticated-orcid":false,"given":"Mathias","family":"Jucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"4272_CR1","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1080\/13506129.2024.2405948","volume":"31","author":"JN Buxbaum","year":"2024","unstructured":"Buxbaum, J. N. et al. Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee. Amyloid 31, 249\u2013256 (2024).","journal-title":"Amyloid"},{"key":"4272_CR2","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1002\/ana.26965","volume":"96","author":"P Chompoopong","year":"2024","unstructured":"Chompoopong, P., Mauermann, M. L., Siddiqi, H. & Peltier, A. Amyloid neuropathy: from pathophysiology to treatment in light-chain amyloidosis and hereditary transthyretin amyloidosis. Ann. Neurol. 96, 423\u2013440 (2024).","journal-title":"Ann. Neurol."},{"key":"4272_CR3","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1001\/jama.2024.0442","volume":"331","author":"FL Ruberg","year":"2024","unstructured":"Ruberg, F. L. & Maurer, M. S. Cardiac amyloidosis due to transthyretin protein: a review. 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A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer\u2019s disease. Nat. Med. 26, 398\u2013407 (2020).","journal-title":"Nat. Med."},{"key":"4272_CR7","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1038\/s41591-022-02074-w","volume":"28","author":"NJ Ashton","year":"2022","unstructured":"Ashton, N. J. et al. Differential roles of Abeta42\/40, p-tau231 and p-tau217 for Alzheimer\u2019s trial selection and disease monitoring. Nat. Med. 28, 2555\u20132562 (2022).","journal-title":"Nat. Med."},{"key":"4272_CR8","doi-asserted-by":"publisher","first-page":"5324","DOI":"10.1002\/alz.13907","volume":"20","author":"A Emersic","year":"2024","unstructured":"Emersic, A. et al. Cerebrospinal fluid p-tau181, 217, and 231 in definite Creutzfeldt\u2013Jakob disease with and without concomitant pathologies. 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