{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T08:58:00Z","timestamp":1776416280952,"version":"3.51.2"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":58,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007566","name":"Royal College of Emergency Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007566","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Albumin versus Balanced Crystalloid"},{"name":"Sepsis Research Fiona Elizabeth Agnew Trust"},{"DOI":"10.13039\/501100023262","name":"Jon Moulton Charity Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023262","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016334","name":"demenTia Research And Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100021573","name":"Norfolk & Suffolk Foundation Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100021573","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018063","name":"Alzheimer\u2019s Research United Kingdom","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute of Health and Care Research","doi-asserted-by":"publisher","award":["NIHR302544"],"award-info":[{"award-number":["NIHR302544"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Following acute infective illness, patients frequently exhibit neurological symptoms, with persistent neurological symptoms commonly observed following severe infection. However, the association between systemic infection and the concentration of blood-based biomarkers of brain injury and the relationship between these and markers of the host response to infection are poorly characterized in the literature. Further, the association between acute illness and the Alzheimer\u2019s disease\u2013associated biomarker phosphorylated-tau-217 (p-tau-217) is unknown. In acute samples from 26 patients attending the emergency department with suspected sepsis (clinically suspected or proven infection, a National Early Warning Score or National Early Warning Score 2 score \u2265 5), the levels of serum biomarkers of brain injury (neurofilament light [NfL], glial fibrillary acidic protein (GFAP), total tau and ubiquitin C-terminal hydrolase L1) and p-tau-217 were compared to age- and sex-matched non-infected controls, with further assessment of the correlation between the biomarker levels and cytokine profiles. p-tau-217 levels were additionally compared to a positive control group of patients with diagnosed Alzheimer\u2019s disease. Both total tau (P = 0.006, Wilcoxon rank-sum test) and NfL (P = 0.044, Wilcoxon rank-sum test) levels were significantly higher in patients with suspected sepsis as compared to controls, with no significant differences in levels of GFAP or ubiquitin C-terminal hydrolase L1. Within suspected sepsis patients, serum total tau levels were associated with multiple cytokines and a summary cytokine score (Spearman\u2019s rank correlation coefficient \u03c1 = 0.65, P &amp;lt; 0.001). There were significantly higher p-tau-217 levels in suspected sepsis patients as compared to non-infected controls (P &amp;lt; 0.001, Dunn\u2013Kruskal\u2013Wallis test), with no significant difference compared to Alzheimer\u2019s disease controls (P = 0.118, Dunn\u2013Kruskal\u2013Wallis test). Of patients with suspected sepsis, 29% had a p-tau-217 level classified as high (&amp;gt;0.63\u2005pg\/ml) with a further 17% classified as intermediate (0.4\u20130.63\u2005pg\/ml). In conclusion, we have identified elevated levels of total tau and NfL compared to age- and sex-matched controls, along with significant correlations between these tau levels and cytokine levels. Additionally, we observed elevated levels of p-tau-217 in the patient cohort, with levels comparable to those seen in Alzheimer\u2019s disease patients. Further analysis is required to replicate the findings of this study in larger cohorts. However, the results suggest a potentially extracranial source of tau expression in the context of infection or physiological stress. Given the potential for acute illness to influence p-tau-217 levels, our results raise important considerations regarding the interpretation of p-tau-217 as a diagnostic marker for Alzheimer\u2019s disease in patients with active infection.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag063","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T12:37:17Z","timestamp":1772195837000},"source":"Crossref","is-referenced-by-count":0,"title":["Brain-injury and Alzheimer\u2019s disease biomarkers are elevated in patients with suspected infection and physiological derangement: importance for context-specific interpretation of Alzheimer\u2019s biomarkers"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0216-1866","authenticated-orcid":false,"given":"Daniel P","family":"Whitehouse","sequence":"first","affiliation":[{"name":"Department of Medicine: Perioperative, Acute, Critical Care and Emergency Medicine (PACE) Section, University of Cambridge ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6926-9508","authenticated-orcid":false,"given":"Jack","family":"Cafferkey","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Royal Infirmary of Edinburgh, Emergency Medicine Research Group Edinburgh (EMERGE) , Edinburgh ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Royal Infirmary of Edinburgh, Emergency Medicine Research Group Edinburgh (EMERGE) , Edinburgh ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soraya","family":"Ebrahimi","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1063-6937","authenticated-orcid":false,"given":"Timothy","family":"Rittman","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hornberger","sequence":"additional","affiliation":[{"name":"Norwich Medical School, University of East Anglia , Norwich ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alasdair","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Royal Infirmary of Edinburgh, Emergency Medicine Research Group Edinburgh (EMERGE) , Edinburgh ,","place":["UK"]},{"name":"Acute Care Edinburgh, Centre for Population and Health Sciences, Usher Institute, University of Edinburgh , Edinburgh 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