{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:41:46Z","timestamp":1790728906378,"version":"4.1.0"},"reference-count":78,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/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":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>With the rapid development of blood biomarkers (BBMs) related to amyloid\u2010\u03b2 (A\u03b2) pathology in Alzheimer's disease (AD), the question arises whether these can replace the accepted reference standard, positron emission tomography (PET), for assessing A\u03b2 burden. BBMs can differentiate A\u03b2 status reliably in cognitively impaired patients, but two\u2010threshold strategies to further improve their performance demonstrate the need for pathological confirmation by A\u03b2\u2010PET in a non\u2010negligible portion of individuals (\u223c10%\u201340%), especially in early\u2010stage disease where BBM performance declines due to lower AD prevalence, reducing the test's positive predictive value (PPV) and increasing the risk for false\u2010positives. This may be increasingly relevant in the future, considering the development of (very) early interventions against AD. Further, BBMs do not accurately reflect the actual A\u03b2 load or change after immunotherapy. Consequently, there are clear remaining needs for A\u03b2\u2010PET in several clinically important settings as (i) a confirmatory test and (ii) to determine treatment response.<\/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>When used as stand\u2010alone tests, blood biomarkers (BBMs) demonstrate good sensitivity and specificity (84%\u201390%) relative to amyloid\u2010\u03b2 positron emission tomography (A\u03b2\u2010PET).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Two\u2010threshold strategies improve BBM performance but require confirmatory testing by, for example, A\u03b2\u2010PET in a non\u2010negligible portion of patients that fall in an intermediate range or \u201cgray\u2010zone\u201d (\u223c10%\u201340%).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In early\/preclinical populations, BBM performance declines due to lower AD prevalence, reducing the test's positive predictive value (PPV) and increases the gray\u2010zone population.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Currently available BBMs cannot reliably estimate A\u03b2\u2010PET burden or track A\u03b2\u2010plaque removal post\u2010immunotherapy.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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