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Here, we find novel evidence that plasma p\u2010tau\n                      <jats:sub>181<\/jats:sub>\n                      is elevated in amyotrophic lateral sclerosis (ALS), a neurodegenerative condition typically lacking tau pathology. We performed a detailed evaluation to identify the clinical correlates of elevated p\u2010tau\n                      <jats:sub>181<\/jats:sub>\n                      in ALS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients were clinically or pathologically diagnosed with ALS (n\u00a0=\u00a0130) or AD (n\u00a0=\u00a079), or were healthy non\u2010impaired controls (n\u00a0=\u00a026). Receiver operating characteristic (ROC) curves were analyzed and area under the curve (AUC) was used to discriminate AD from ALS. Within ALS, Mann\u2013Whitney\u2013Wilcoxon tests compared analytes by presence\/absence of upper motor neuron and lower motor neuron (LMN) signs. Spearman correlations tested associations between plasma p\u2010tau\n                      <jats:sub>181<\/jats:sub>\n                      and postmortem neuron loss.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A Wilcoxon test showed plasma p\u2010tau\n                      <jats:sub>181<\/jats:sub>\n                      was higher in ALS than controls (\n                      <jats:italic>W<\/jats:italic>\n                      \u00a0=\u00a02,600,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.000015), and ROC analyses showed plasma p\u2010tau\n                      <jats:sub>181<\/jats:sub>\n                      poorly discriminated AD and ALS (AUC\u00a0=\u00a00.60). In ALS, elevated plasma p\u2010tau\n                      <jats:sub>181<\/jats:sub>\n                      was associated with LMN signs in cervical (\n                      <jats:italic>W<\/jats:italic>\n                      \u00a0=\u00a0827,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0072), thoracic (\n                      <jats:italic>W<\/jats:italic>\n                      \u00a0=\u00a0469,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.00025), and lumbosacral regions (\n                      <jats:italic>W<\/jats:italic>\n                      \u00a0=\u00a0851,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0000029). In support of LMN findings, plasma p\u2010tau\n                      <jats:sub>181<\/jats:sub>\n                      was associated with neuron loss in the spinal cord (rho\u00a0=\u00a00.46,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.017), but not in the motor cortex (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.41). Cerebrospinal spinal fluid p\u2010tau\n                      <jats:sub>181<\/jats:sub>\n                      and plasma neurofilament light chain were included as reference analytes, and demonstrate specificity of findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      We found strong evidence that plasma p\u2010tau\n                      <jats:sub>181<\/jats:sub>\n                      is elevated in ALS and may be a novel marker specific to LMN dysfunction. ANN NEUROL 2022;92:807\u2013818\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26462","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T13:59:00Z","timestamp":1658757540000},"page":"807-818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Elevated Plasma Phosphorylated Tau 181 in Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-2766","authenticated-orcid":false,"given":"Katheryn A. 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