{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T09:14:21Z","timestamp":1783415661906,"version":"3.54.6"},"reference-count":32,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Blood-based biomarkers are increasingly used as scalable front-line tools for Alzheimer's disease amyloid evaluation, but most are validated against amyloid positron emission tomography (PET) and\/or cerebrospinal fluid (CSF) rather than neuropathology. In a chained validation cascade (neuropathology\u2192PET\u2192CSF\u2192blood), reported performance may depend strongly on the comparator and on how \u201cgray-zone\u201d (indeterminate) results are handled.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To quantify benchmark dependence and gray-zone policy sensitivity in amyloid biomarker validation and characterize plasma-to-neuropathology performance inference from imperfect proxies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assembled a fully auditable evidence core spanning the amyloid cascade with reconstructable 2\u2009\u00d7\u20092 tables. We recomputed positive percent agreement (PPA) and negative percent agreement (NPA) with 95% Wilson confidence intervals under a prespecified primary policy (exclude indeterminates) and two sensitivity policies (indeterminate\u2192negative; indeterminate\u2192positive). Reference-swap drift across benchmarks was summarized with Monte Carlo uncertainty intervals. For plasma-to-neuropathology inference, we combined plasma-PET agreement with tracer-specific PET-autopsy anchors and reported (i) chained-proxy point implications under conditional independence and (ii) partial-identification bounds without conditional independence across prevalence scenarios (\u03c0\u2009=\u200910\u201350%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Under the primary policy, Lumipulse plasma pTau217\/A\u03b242 showed similar agreement across PET, CSF, and composite comparators (PPA 0.97\u20130.98; NPA \u22480.91), with drift intervals spanning zero. Indeterminates were frequent (\u223c19\u201320%) and dominated apparent shifts: indeterminate\u2192negative reduced PPA by 0.13\u20130.21, whereas indeterminate\u2192positive reduced NPA by 0.17\u20130.21. Chained-proxy implications for plasma versus neuropathology varied by PET tracer anchor (sensitivity 0.86\u20130.96; specificity 0.81\u20130.91), while bounds were wider (sensitivity 0.83\u20131.00; specificity 0.81\u20130.98).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Gray-zone policy is a first-order driver of reported blood-test performance, and proxy-to-proxy agreement does not uniquely identify plasma-to-neuropathology accuracy without explicit assumptions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261430858","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T05:16:27Z","timestamp":1774242987000},"page":"184-198","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["From autopsy to PET to cerebrospinal fluid to blood: Quantifying reference-standard dependence in Alzheimer's disease amyloid biomarker validation"],"prefix":"10.1177","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3857-6887","authenticated-orcid":false,"given":"Khushboo","family":"Verma","sequence":"first","affiliation":[{"name":"University of Texas at Tyler"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9054-2123","authenticated-orcid":false,"given":"Satwant","family":"Kumar","sequence":"additional","affiliation":[{"name":"Alzheimer's Alliance of Smith County, Tyler, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,22]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000214441"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2014.18.6.447"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12748"},{"key":"e_1_3_3_5_2","first-page":"1797","article-title":"Plasma p-tau231 and p-tau217 as state markers of amyloid-\u03b2 pathology in preclinical Alzheimer\u2019s disease","volume":"28","author":"Mil\u00e0-Alom\u00e0 M","year":"2022","unstructured":"Mil\u00e0-Alom\u00e0 M, Ashton NJ, Shekari M, et al. Plasma p-tau231 and p-tau217 as state markers of amyloid-\u03b2 pathology in preclinical Alzheimer\u2019s disease. Nat Med 2022; 28: 1797\u20131801.","journal-title":"Nat Med"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2023.30"},{"key":"e_1_3_3_7_2","article-title":"Alzheimer\u2019s Association Clinical Practice Guideline on the use of blood-based biomarkers in the diagnostic workup of suspected Alzheimer\u2019s disease within specialized care settings","volume":"21","author":"Palmqvist S","year":"2025","unstructured":"Palmqvist S, Whitson HE, Allen LA, et al. Alzheimer\u2019s Association Clinical Practice Guideline on the use of blood-based biomarkers in the diagnostic workup of suspected Alzheimer\u2019s disease within specialized care settings. Alzheimers Dement 2025; 21: e70535.","journal-title":"Alzheimers Dement"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70142-4"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25456"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.2814"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12756"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-012799"},{"key":"e_1_3_3_13_2","article-title":"STARD 2015: An updated list of essential items for reporting diagnostic accuracy studies","volume":"351","author":"Bossuyt PM","year":"2015","unstructured":"Bossuyt PM, Reitsma JB, Bruns DE, et al. STARD 2015: An updated list of essential items for reporting diagnostic accuracy studies. Br Med J 2015; 351: h5527.","journal-title":"Br Med J"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-023-01873-0"},{"key":"e_1_3_3_15_2","unstructured":"Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests - Guidance for Industry and FDA Staff | FDA https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/statistical-guidance-reporting-results-studies-evaluating-diagnostic-tests-guidance-industry-and-fda (accessed 21 December 2025)."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.4144"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.02.004"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.8392"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13764"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14338"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-025-02557-7"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7688"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3310\/hta11500"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.02.005"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6803"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4444"},{"key":"e_1_3_3_28_2","article-title":"Diagnostic test evaluation methodology: a systematic review of methods employed to evaluate diagnostic tests in the absence of gold standard \u2013 an update","volume":"14","author":"Chikere CMU","year":"2019","unstructured":"Chikere CMU, Wilson K, Graziadio S, et al. Diagnostic test evaluation methodology: a systematic review of methods employed to evaluate diagnostic tests in the absence of gold standard \u2013 an update. PLoS One 2019; 14: e0223832.","journal-title":"PLoS One"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(25)00070-2"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-155-8-201110180-00009"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-014-0241-z"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8086"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2673"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261430858","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13872877261430858","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261430858","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T08:24:14Z","timestamp":1783412654000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13872877261430858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,22]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1177\/13872877261430858"],"URL":"https:\/\/doi.org\/10.1177\/13872877261430858","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,22]]}}}