{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:43:56Z","timestamp":1790837036227,"version":"4.1.0"},"reference-count":127,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>The revised biomarker framework for diagnosis and staging of Alzheimer's disease (AD) relies on amyloid beta (A\u03b2) and tau pathologies as core markers, and markers for adjacent pathophysiology, such as neurodegeneration and inflammation. Many of the core fluid biomarkers are phosphorylated tau (p\u2010tau) fragments, with p\u2010tau217 showing a prominent association with A\u03b2 and tau. While positron emission tomography (PET) imaging is well established, plasma p\u2010tau assays are newer and likely to reduce the use of expensive, and less accessible cerebrospinal fluid and PET imaging tests, thereby promoting wider access to AD screening. There is a need for greater understanding of how the various plasma p\u2010tau species reflect different pathological processes of AD and how different immunoassays perform. This review surveys the available immunoassays and highlights their strengths and limitations in different contexts of use. Assays need to be standardized to maximize their impact on AD clinical research, and patient diagnosis and management.<\/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>Different plasma phosphorylated tau (p\u2010tau) species reflect different pathological processes of Alzheimer's disease (AD), with p\u2010tau231 showing the greatest association with the earliest increases in brain amyloid beta (A\u03b2) accumulation, while p\u2010tau217 shows greater association with both brain A\u03b2 and early tau pathology, and other p\u2010tau and tau fragment species show greater association with later stages of brain tau pathology.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma p\u2010tau217 has proven to be an excellent biomarker for AD pathology due to its close association with both brain A\u03b2 and tau pathology, as well as its large dynamic range.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Many different assays with varying performance exist for the same p\u2010tau species, with mass spectrometry assays performing uniformly well, and several immunoassays achieving comparable performance.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\u201cRound robin\u201d head\u2010to\u2010head studies have been performed to compare different assays for several key plasma biomarkers, including p\u2010tau181 and p\u2010tau217, but additional head\u2010to\u2010head studies are needed, especially for new analytes and for measuring performance in diverse populations.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma immunoassays have the potential to increase accessibility of early diagnostic testing for a broad population, including diverse historically under\u2010represented and under\u2010served populations, due to the potential to be implemented globally, including in primary care settings; however, further research is needed to validate the optimal cutoffs for each assay for real\u2010world clinical usage.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Eventually, clinical implementation of a two\u2010step workflow may allow standalone use of plasma testing in certain contexts, minimizing the need for confirmation with costly and less accessible cerebrospinal fluid\/positron emission tomography testing.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n   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