{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T23:48:29Z","timestamp":1793922509078,"version":"4.8.0"},"reference-count":126,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eBioMedicine"],"published-print":{"date-parts":[[2024,10]]},"DOI":"10.1016\/j.ebiom.2024.105322","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T18:31:46Z","timestamp":1727980306000},"page":"105322","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":58,"special_numbering":"C","title":["Insights into the use of biomarkers in clinical trials in Alzheimer's disease"],"prefix":"10.1016","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9057-8014","authenticated-orcid":false,"given":"Tharick A.","family":"Pascoal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiano S.","family":"Aguzzoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firoza Z.","family":"Lussier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Crivelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5942-4778","authenticated-orcid":false,"given":"Claudia K.","family":"Suemoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Fortea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Rosa-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo R.","family":"Zimmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela C.L.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2212-3373","authenticated-orcid":false,"given":"Bruna","family":"Bellaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1474-4422(12)70291-0","article-title":"Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers","volume":"12","author":"Jack","year":"2013","journal-title":"Lancet Neurol"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib2","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer's disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol"},{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib3","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/cts.12491","article-title":"Lessons learned from Alzheimer disease: clinical trials with negative outcomes","volume":"11","author":"Cummings","year":"2018","journal-title":"Clin Transl Sci"},{"key":"10.1016\/j.ebiom.2024.105322_bib4","series-title":"BEST (Biomarkers, EndpointS, and other Tools) resource","year":"2016"},{"issue":"3","key":"10.1016\/j.ebiom.2024.105322_bib5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/1535370217750088","article-title":"Biomarker definitions and their applications","volume":"243","author":"Califf","year":"2018","journal-title":"Exp Biol Med (Maywood)"},{"key":"10.1016\/j.ebiom.2024.105322_bib6","series-title":"Context of use","year":"2021"},{"issue":"7","key":"10.1016\/j.ebiom.2024.105322_bib7","doi-asserted-by":"crossref","first-page":"952","DOI":"10.3390\/medicina58070952","article-title":"Biomarkers for Alzheimer's disease: context of use, qualification, and roadmap for clinical implementation","volume":"58","author":"Cummings","year":"2022","journal-title":"Medicina (Kaunas)"},{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib8","article-title":"Alzheimer's disease drug development pipeline: 2024","volume":"10","author":"Cummings","year":"2024","journal-title":"Alzheimers Dement (N Y)"},{"key":"10.1016\/j.ebiom.2024.105322_bib9","series-title":"National cancer institute","year":"2011"},{"issue":"3","key":"10.1016\/j.ebiom.2024.105322_bib10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1365-2796.2004.01388.x","article-title":"Mild cognitive impairment as a diagnostic entity","volume":"256","author":"Petersen","year":"2004","journal-title":"J\u00a0Intern Med"},{"issue":"6","key":"10.1016\/j.ebiom.2024.105322_bib11","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.jalz.2014.01.001","article-title":"A\u00a0conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease","volume":"10","author":"Jessen","year":"2014","journal-title":"Alzheimers Dement"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib12","doi-asserted-by":"crossref","first-page":"e397","DOI":"10.1212\/WNL.0000000000008838","article-title":"Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration","volume":"94","author":"Thomas","year":"2020","journal-title":"Neurology"},{"issue":"3","key":"10.1016\/j.ebiom.2024.105322_bib13","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward defining the preclinical stages of Alzheimer's disease: recommendations from the national institute on aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimers Dement"},{"key":"10.1016\/j.ebiom.2024.105322_bib14","series-title":"Diagnostic and statistical manual of mental disorders: DSM-5","author":"American Psychiatric Association","year":"2013"},{"key":"10.1016\/j.ebiom.2024.105322_bib15","series-title":"Early Alzheimer's disease: developing drugs for treatment","year":"2024"},{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib16","first-page":"197","article-title":"Two randomized phase 3 studies of Aducanumab in early Alzheimer's disease","volume":"9","author":"Budd","year":"2022","journal-title":"J\u00a0Prev Alzheimers Dis"},{"issue":"20","key":"10.1016\/j.ebiom.2024.105322_bib17","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1056\/NEJMoa2304430","article-title":"Two phase 3 trials of gantenerumab in early Alzheimer's disease","volume":"389","author":"Bateman","year":"2023","journal-title":"N\u00a0Engl J Med"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib18","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer's disease","volume":"388","author":"van Dyck","year":"2023","journal-title":"N\u00a0Engl J Med"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib19","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13195-018-0424-5","article-title":"Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab\u00a0anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild-to-moderate Alzheimer's disease (BLAZE)","volume":"10","author":"Salloway","year":"2018","journal-title":"Alzheimers Res Ther"},{"issue":"21","key":"10.1016\/j.ebiom.2024.105322_bib20","doi-asserted-by":"crossref","first-page":"e1889","DOI":"10.1212\/WNL.0000000000005550","article-title":"ABBY: a phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease","volume":"90","author":"Cummings","year":"2018","journal-title":"Neurology"},{"issue":"12","key":"10.1016\/j.ebiom.2024.105322_bib21","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1056\/NEJMoa2305032","article-title":"Trial of solanezumab in preclinical Alzheimer's disease","volume":"389","author":"Sperling","year":"2023","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.ebiom.2024.105322_bib22","first-page":"802","article-title":"Diagnoses, syndromes, and diseases: a knowledge representation problem","volume":"2003","author":"Calvo","year":"2003","journal-title":"AMIA Annu Symp Proc"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib23","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jalz.2018.11.002","article-title":"\u201cAlzheimer's disease\u201d is neither \u201cAlzheimer's clinical syndrome\u201d nor \u201cdementia\u201d","volume":"15","author":"Jagust","year":"2019","journal-title":"Alzheimers Dement"},{"issue":"3","key":"10.1016\/j.ebiom.2024.105322_bib24","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/S1474-4422(20)30440-3","article-title":"New insights into atypical Alzheimer's disease in the era of biomarkers","volume":"20","author":"Graff-Radford","year":"2021","journal-title":"Lancet Neurol"},{"issue":"4 Movement Disorders","key":"10.1016\/j.ebiom.2024.105322_bib25","first-page":"1117","article-title":"Diagnostic approach to atypical parkinsonian syndromes","volume":"22","author":"McFarland","year":"2016","journal-title":"Continuum (Minneap Minn)"},{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib26","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S1474-4422(03)00305-3","article-title":"Vascular cognitive impairment","volume":"2","author":"O'Brien","year":"2003","journal-title":"Lancet Neurol"},{"issue":"3","key":"10.1016\/j.ebiom.2024.105322_bib27","doi-asserted-by":"crossref","first-page":"929","DOI":"10.3233\/JAD-160979","article-title":"The mild behavioral impairment checklist (MBI-C): a rating scale for neuropsychiatric symptoms in pre-dementia populations","volume":"56","author":"Ismail","year":"2017","journal-title":"J\u00a0Alzheimers Dis"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib28","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-beta and tau: the trigger and bullet in Alzheimer disease pathogenesis","volume":"71","author":"Bloom","year":"2014","journal-title":"JAMA Neurol"},{"issue":"5","key":"10.1016\/j.ebiom.2024.105322_bib29","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1212\/WNL.0000000000002923","article-title":"A\/T\/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers","volume":"87","author":"Jack","year":"2016","journal-title":"Neurology"},{"issue":"9","key":"10.1016\/j.ebiom.2024.105322_bib30","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/s43587-023-00471-5","article-title":"A\u00a0two-step workflow based on plasma p-tau217 to screen for amyloid \u03b2 positivity with further confirmatory testing only in uncertain cases","volume":"3","author":"Brum","year":"2023","journal-title":"Nature Aging"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib31","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1038\/s41591-024-02869-z","article-title":"Highly accurate blood test for Alzheimer's disease comparable or superior to clinical CSF tests","volume":"30","author":"Barthelemy","year":"2024","journal-title":"Nat Med"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib32","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0197-4580(97)00056-0","article-title":"Frequency of stages of Alzheimer-related lesions in different age categories","volume":"18","author":"Braak","year":"1997","journal-title":"Neurobiol Aging"},{"issue":"9","key":"10.1016\/j.ebiom.2024.105322_bib33","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1093\/brain\/awaa180","article-title":"18F-MK-6240 PET for early and late detection of neurofibrillary tangles","volume":"143","author":"Pascoal","year":"2020","journal-title":"Brain"},{"issue":"11","key":"10.1016\/j.ebiom.2024.105322_bib34","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1038\/s41591-022-02049-x","article-title":"Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline","volume":"28","author":"Ossenkoppele","year":"2022","journal-title":"Nat Med"},{"issue":"3","key":"10.1016\/j.ebiom.2024.105322_bib35","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the national institute on aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimers Dement"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","article-title":"National institute on aging-Alzheimer's association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach","volume":"123","author":"Montine","year":"2012","journal-title":"Acta Neuropathol"},{"issue":"16","key":"10.1016\/j.ebiom.2024.105322_bib37","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aaz2387","article-title":"A\u03b2 deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer's disease","volume":"6","author":"Mattsson-Carlgren","year":"2020","journal-title":"Sci Adv"},{"issue":"6","key":"10.1016\/j.ebiom.2024.105322_bib38","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/s43587-022-00204-0","article-title":"Biomarker modeling of Alzheimer's disease using PET-based Braak staging","volume":"2","author":"Therriault","year":"2022","journal-title":"Nature Aging"},{"issue":"Pt 5","key":"10.1016\/j.ebiom.2024.105322_bib39","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1093\/brain\/aww023","article-title":"Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages","volume":"139","author":"Schwarz","year":"2016","journal-title":"Brain"},{"issue":"9","key":"10.1016\/j.ebiom.2024.105322_bib40","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1001\/jamaneurol.2023.2338","article-title":"Prevalence and clinical implications of a beta-amyloid-negative, tau-positive cerebrospinal fluid biomarker profile in alzheimer disease","volume":"80","author":"Erickson","year":"2023","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.ebiom.2024.105322_bib41","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.neurobiolaging.2021.09.019","article-title":"Abnormal tau in amyloid PET negative individuals","volume":"109","author":"Yoon","year":"2022","journal-title":"Neurobiol Aging"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib42","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jalz.2013.03.007","article-title":"Designing drug trials for Alzheimer's disease: what we have learned from the release of the phase III antibody trials: a report from the EU\/US\/CTAD Task Force","volume":"9","author":"Vellas","year":"2013","journal-title":"Alzheimers Dement"},{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib43","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/ana.24188","article-title":"A\u00a0critique of the drug discovery and phase 3 clinical programs targeting the amyloid hypothesis for Alzheimer disease","volume":"76","author":"Karran","year":"2014","journal-title":"Ann Neurol"},{"issue":"10062","key":"10.1016\/j.ebiom.2024.105322_bib44","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1016\/S0140-6736(16)31275-2","article-title":"Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial","volume":"388","author":"Gauthier","year":"2016","journal-title":"Lancet"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib45","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1097\/NEN.0b013e31824b211b","article-title":"Accuracy of the clinical diagnosis of Alzheimer disease at national Institute on aging Alzheimer disease centers, 2005-2010","volume":"71","author":"Beach","year":"2012","journal-title":"J\u00a0Neuropathol Exp Neurol"},{"issue":"6","key":"10.1016\/j.ebiom.2024.105322_bib46","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1001\/jama.2023.13239","article-title":"Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial","volume":"330","author":"Sims","year":"2023","journal-title":"JAMA"},{"issue":"18","key":"10.1016\/j.ebiom.2024.105322_bib47","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMoa2100708","article-title":"Donanemab in early Alzheimer's disease","volume":"384","author":"Mintun","year":"2021","journal-title":"N\u00a0Engl J Med"},{"issue":"24","key":"10.1016\/j.ebiom.2024.105322_bib48","doi-asserted-by":"crossref","first-page":"e3257","DOI":"10.1212\/WNL.0000000000010943","article-title":"\u03b2-Amyloid and tau biomarkers and clinical phenotype in dementia with Lewy bodies","volume":"95","author":"Ferreira","year":"2020","journal-title":"Neurology"},{"issue":"7","key":"10.1016\/j.ebiom.2024.105322_bib49","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1038\/s41591-023-02380-x","article-title":"Astrocyte reactivity influences amyloid-beta effects on tau pathology in preclinical Alzheimer's disease","volume":"29","author":"Bellaver","year":"2023","journal-title":"Nat Med"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib50","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1093\/brain\/awac329","article-title":"Phospho-tau with subthreshold tau-PET predicts increased tau accumulation rates in amyloid-positive individuals","volume":"146","author":"Groot","year":"2022","journal-title":"Brain"},{"issue":"11","key":"10.1016\/j.ebiom.2024.105322_bib51","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.1093\/brain\/awab248","article-title":"Longitudinal 18F-MK-6240 tau tangles accumulation follows Braak stages","volume":"144","author":"Pascoal","year":"2021","journal-title":"Brain"},{"issue":"6","key":"10.1016\/j.ebiom.2024.105322_bib52","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1002\/alz.12875","article-title":"Tau-PET is superior to phospho-tau when predicting cognitive decline in symptomatic AD patients","volume":"19","author":"Smith","year":"2023","journal-title":"Alzheimers Dement"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib53","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/alz.12748","article-title":"The AHEAD 3-45 study: design of a prevention trial for Alzheimer's disease","volume":"19","author":"Rafii","year":"2023","journal-title":"Alzheimers Dement"},{"issue":"6","key":"10.1016\/j.ebiom.2024.105322_bib54","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s00259-018-3933-3","article-title":"Amyloid and tau signatures of brain metabolic decline in preclinical Alzheimer's disease","volume":"45","author":"Pascoal","year":"2018","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"10","key":"10.1016\/j.ebiom.2024.105322_bib55","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/s43587-023-00490-2","article-title":"APOEepsilon4 potentiates amyloid beta effects on longitudinal tau pathology","volume":"3","author":"Ferrari-Souza","year":"2023","journal-title":"Nat Aging"},{"issue":"3","key":"10.1016\/j.ebiom.2024.105322_bib56","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1002\/alz.13532","article-title":"Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired APOE epsilon4 homozygotes","volume":"20","author":"Riviere","year":"2024","journal-title":"Alzheimers Dement"},{"key":"10.1016\/j.ebiom.2024.105322_bib57","series-title":"MCLENA-1: a clinical trial for the assessment of lenalidomide in amnestic MCI patients","year":"2024"},{"key":"10.1016\/j.ebiom.2024.105322_bib58","series-title":"Safety and pharmacokinetics of single ascending doses and multiple ascending doses of CS6253 in healthy volunteers","year":"2024"},{"key":"10.1016\/j.ebiom.2024.105322_bib59","series-title":"Allopregnanolone regenerative therapeutic for mild Alzheimer's disease","author":"ClinicalTrials gov","year":"2023"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib60","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1038\/s41598-018-37769-z","article-title":"For Alzheimer's disease neuroimaging I. predicting Alzheimer's disease progression using multi-modal deep learning approach","volume":"9","author":"Lee","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib61","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13195-018-0392-9","article-title":"Discovery and validation of autosomal dominant Alzheimer's disease mutations","volume":"10","author":"Hsu","year":"2018","journal-title":"Alzheimers Res Ther"},{"issue":"19","key":"10.1016\/j.ebiom.2024.105322_bib62","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1056\/NEJM199511093331902","article-title":"Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein","volume":"333","author":"Polvikoski","year":"1995","journal-title":"N\u00a0Engl J Med"},{"issue":"5","key":"10.1016\/j.ebiom.2024.105322_bib63","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/s41591-024-02931-w","article-title":"APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease","volume":"30","author":"Fortea","year":"2024","journal-title":"Nat Med"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib64","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1021\/jm301297f","article-title":"Demystifying brain penetration in central nervous system drug discovery. Miniperspective","volume":"56","author":"Di","year":"2013","journal-title":"J\u00a0Med Chem"},{"issue":"6","key":"10.1016\/j.ebiom.2024.105322_bib65","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nrd4309","article-title":"Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework","volume":"13","author":"Cook","year":"2014","journal-title":"Nat Rev Drug Discov"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib66","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/nchembio.1211","article-title":"Determining target engagement in living systems","volume":"9","author":"Simon","year":"2013","journal-title":"Nat Chem Biol"},{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib67","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1365-2125.2011.04085.x","article-title":"Positron emission tomography molecular imaging for drug development","volume":"73","author":"Matthews","year":"2012","journal-title":"Br J Clin Pharmacol"},{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib68","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/ana.25513","article-title":"Target engagement in an alzheimer trial: crenezumab lowers amyloid beta oligomers in cerebrospinal fluid","volume":"86","author":"Yang","year":"2019","journal-title":"Ann Neurol"},{"issue":"6","key":"10.1016\/j.ebiom.2024.105322_bib69","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1038\/s41591-023-02326-3","article-title":"Tau-targeting antisense oligonucleotide MAPT(Rx) in mild Alzheimer's disease: a phase 1b, randomized, placebo-controlled trial","volume":"29","author":"Mummery","year":"2023","journal-title":"Nat Med"},{"issue":"8","key":"10.1016\/j.ebiom.2024.105322_bib70","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1001\/jamaneurol.2022.1375","article-title":"Safety and efficacy of Semorinemab in individuals with prodromal to mild Alzheimer disease: a randomized clinical trial","volume":"79","author":"Teng","year":"2022","journal-title":"JAMA Neurol"},{"issue":"12","key":"10.1016\/j.ebiom.2024.105322_bib71","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1038\/s43587-023-00523-w","article-title":"TANGO: a placebo-controlled randomized phase 2 study of efficacy and safety of the anti-tau monoclonal antibody gosuranemab in early Alzheimer's disease","volume":"3","author":"Shulman","year":"2023","journal-title":"Nat Aging"},{"issue":"9","key":"10.1016\/j.ebiom.2024.105322_bib72","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1002\/alz.12321","article-title":"Visualization of neurofibrillary tangle maturity in Alzheimer's disease: a clinicopathologic perspective for biomarker research","volume":"17","author":"Moloney","year":"2021","journal-title":"Alzheimers Dement"},{"issue":"11","key":"10.1016\/j.ebiom.2024.105322_bib73","doi-asserted-by":"crossref","DOI":"10.1016\/j.drudis.2022.103338","article-title":"A\u00a0call for better understanding of target engagement in Tau antibody development","volume":"27","author":"Bespalov","year":"2022","journal-title":"Drug Discov Today"},{"issue":"7","key":"10.1016\/j.ebiom.2024.105322_bib74","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/nrd.2016.88","article-title":"Failed trials for central nervous system disorders do not necessarily invalidate preclinical models and drug targets","volume":"15","author":"Bespalov","year":"2016","journal-title":"Nat Rev Drug Discov"},{"issue":"9-10","key":"10.1016\/j.ebiom.2024.105322_bib75","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.drudis.2011.12.020","article-title":"Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving phase II survival","volume":"17","author":"Morgan","year":"2012","journal-title":"Drug Discov Today"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib76","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.bbr.2008.02.016","article-title":"Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior","volume":"192","author":"Selkoe","year":"2008","journal-title":"Behav Brain Res"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib77","article-title":"Tau oligomers neurotoxicity","volume":"11","author":"Niewiadomska","year":"2021","journal-title":"Life (Basel)"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib78","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13195-020-00663-w","article-title":"Aducanumab, gantenerumab, BAN2401, and ALZ-801-the first wave of amyloid-targeting drugs for Alzheimer's disease with potential for near term approval","volume":"12","author":"Tolar","year":"2020","journal-title":"Alzheimer's Res Ther"},{"issue":"12","key":"10.1016\/j.ebiom.2024.105322_bib79","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41582-023-00883-2","article-title":"Tau-targeting therapies for Alzheimer disease: current status and future directions","volume":"19","author":"Congdon","year":"2023","journal-title":"Nat Rev Neurol"},{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib80","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/brain\/awaa373","article-title":"CSF tau microtubule binding region identifies tau tangle and clinical stages of Alzheimer's disease","volume":"144","author":"Horie","year":"2021","journal-title":"Brain"},{"issue":"8","key":"10.1016\/j.ebiom.2024.105322_bib81","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1212\/WNL.0000000000001877","article-title":"Amyloid-beta 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials","volume":"85","author":"Liu","year":"2015","journal-title":"Neurology"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib82","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1056\/NEJMoa2308719","article-title":"Ultrasound blood-brain barrier opening and Aducanumab in Alzheimer's disease","volume":"390","author":"Rezai","year":"2024","journal-title":"N\u00a0Engl J Med"},{"issue":"8","key":"10.1016\/j.ebiom.2024.105322_bib83","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nrd4051","article-title":"Validating therapeutic targets through human genetics","volume":"12","author":"Plenge","year":"2013","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib84","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13195-021-00813-8","article-title":"A\u00a0randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Abeta protofibril antibody","volume":"13","author":"Swanson","year":"2021","journal-title":"Alzheimers Res Ther"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib85","first-page":"3","article-title":"Thirty-six-month amyloid positron emission tomography results show continued reduction in amyloid burden with subcutaneous gantenerumab","volume":"8","author":"Klein","year":"2021","journal-title":"J\u00a0Prev Alzheimers Dis"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib86","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1056\/NEJMoa1705971","article-title":"Trial of solanezumab for mild dementia due to Alzheimer's disease","volume":"378","author":"Honig","year":"2018","journal-title":"N\u00a0Engl J Med"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib87","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1312889","article-title":"Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease","volume":"370","author":"Doody","year":"2014","journal-title":"N\u00a0Engl J Med"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib88","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13195-017-0318-y","article-title":"A\u00a0phase III randomized trial of gantenerumab in prodromal Alzheimer's disease","volume":"9","author":"Ostrowitzki","year":"2017","journal-title":"Alzheimers Res Ther"},{"issue":"7","key":"10.1016\/j.ebiom.2024.105322_bib89","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/s41591-021-01369-8","article-title":"A\u00a0trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease","volume":"27","author":"Salloway","year":"2021","journal-title":"Nat Med"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib90","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1056\/NEJMoa1304839","article-title":"Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease","volume":"370","author":"Salloway","year":"2014","journal-title":"N\u00a0Engl J Med"},{"issue":"11","key":"10.1016\/j.ebiom.2024.105322_bib91","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1001\/jamaneurol.2022.2909","article-title":"Evaluating the safety and efficacy of crenezumab vs placebo in adults with early alzheimer disease: two phase 3 randomized placebo-controlled trials","volume":"79","author":"Ostrowitzki","year":"2022","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.ebiom.2024.105322_bib92","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ebiom.2016.03.035","article-title":"The role of amyloid-\u03b2 oligomers in toxicity, propagation, and immunotherapy","volume":"6","author":"Sengupta","year":"2016","journal-title":"eBioMedicine"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib93","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13195-017-0253-y","article-title":"Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain","volume":"9","author":"Ng","year":"2017","journal-title":"Alzheimer's Res Ther"},{"issue":"12","key":"10.1016\/j.ebiom.2024.105322_bib94","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1001\/jamaneurol.2022.3392","article-title":"Association of Donanemab treatment with exploratory plasma biomarkers in early symptomatic alzheimer disease: a secondary analysis of the TRAILBLAZER-ALZ randomized clinical trial","volume":"79","author":"Pontecorvo","year":"2022","journal-title":"JAMA Neurol"},{"issue":"3","key":"10.1016\/j.ebiom.2024.105322_bib95","article-title":"Lecanemab reduces brain amyloid-beta and delays cognitive worsening","volume":"4","author":"Knopman","year":"2023","journal-title":"Cell Rep Med"},{"issue":"6","key":"10.1016\/j.ebiom.2024.105322_bib96","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1001\/jamaneurol.2024.0991","article-title":"Downstream biomarker effects of gantenerumab or solanezumab in dominantly inherited alzheimer disease: the DIAN-TU-001 randomized clinical trial","volume":"81","author":"Wagemann","year":"2024","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.ebiom.2024.105322_bib97","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2023.104923","article-title":"Efficacy assessment of an active tau immunotherapy in Alzheimer's disease patients with amyloid and tau pathology: a post hoc analysis of the \"ADAMANT\" randomised, placebo-controlled, double-blind, multi-centre, phase 2 clinical trial","volume":"99","author":"Cullen","year":"2024","journal-title":"eBioMedicine"},{"issue":"S24","key":"10.1016\/j.ebiom.2024.105322_bib98","doi-asserted-by":"crossref","DOI":"10.1002\/alz.083153","article-title":"Significant dose-dependent reduction in neurofilament light chain concentration in plasma with oral tau aggregation inhibitor hydromethylthionine mesylate","volume":"19","author":"Wischik","year":"2023","journal-title":"Alzheimers Dementia"},{"key":"10.1016\/j.ebiom.2024.105322_bib99","series-title":"N-terminal tau antibodies fade, Mid-domain ones push to the fore","author":"AlzForum","year":"2021"},{"issue":"6","key":"10.1016\/j.ebiom.2024.105322_bib100","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.jval.2015.08.006","article-title":"Clinical outcome assessments: conceptual foundation-report of the ISPOR clinical outcomes assessment - emerging good practices for outcomes research task force","volume":"18","author":"Walton","year":"2015","journal-title":"Value Health"},{"key":"10.1016\/j.ebiom.2024.105322_bib101","series-title":"Surrogate endpoint resources for drug and biologic development","year":"2018"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib102","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1002\/pst.2219","article-title":"Informed decision-making: statistical methodology for surrogacy evaluation and its role in licensing and reimbursement assessments","volume":"21","author":"Weir","year":"2022","journal-title":"Pharm Stat"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib103","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/bimj.201400049","article-title":"Statistical evaluation of surrogate endpoints with examples from cancer clinical trials","volume":"58","author":"Buyse","year":"2016","journal-title":"Biom J"},{"issue":"15","key":"10.1016\/j.ebiom.2024.105322_bib104","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1056\/NEJMoa010957","article-title":"A\u00a0pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients","volume":"345","author":"Sargent","year":"2001","journal-title":"N\u00a0Engl J Med"},{"issue":"12","key":"10.1016\/j.ebiom.2024.105322_bib105","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1001\/jama.2020.1176","article-title":"When can intermediate outcomes Be used as surrogate outcomes?","volume":"323","author":"DeMets","year":"2020","journal-title":"JAMA"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib106","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/sim.4780080407","article-title":"Surrogate endpoints in clinical trials: definition and operational criteria","volume":"8","author":"Prentice","year":"1989","journal-title":"Stat Med"},{"issue":"25","key":"10.1016\/j.ebiom.2024.105322_bib107","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1002\/sim.5403","article-title":"Biomarkers and surrogate endpoints in clinical trials","volume":"31","author":"Fleming","year":"2012","journal-title":"Stat Med"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib108","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1377\/hlthaff.24.1.67","article-title":"Surrogate endpoints and FDA's accelerated approval process","volume":"24","author":"Fleming","year":"2005","journal-title":"Health Aff (Millwood)"},{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib109","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1602\/neurorx.1.2.189","article-title":"Biomarkers and surrogate markers: an FDA perspective","volume":"1","author":"Katz","year":"2004","journal-title":"NeuroRx"},{"key":"10.1016\/j.ebiom.2024.105322_bib110","series-title":"Fundamentals of clinical trials","author":"Friedman","year":"2015"},{"issue":"6","key":"10.1016\/j.ebiom.2024.105322_bib111","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1001\/jamaoncol.2017.5618","article-title":"A\u00a025-year experience of US food and drug administration accelerated approval of malignant hematology and oncology drugs and biologics: a review","volume":"4","author":"Beaver","year":"2018","journal-title":"JAMA Oncol"},{"issue":"5","key":"10.1016\/j.ebiom.2024.105322_bib112","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1007\/s43441-022-00430-z","article-title":"Analysis of FDA's accelerated approval program performance December 1992-December 2021","volume":"56","author":"Beakes-Read","year":"2022","journal-title":"Ther Innov Regul Sci"},{"issue":"12","key":"10.1016\/j.ebiom.2024.105322_bib113","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1056\/NEJMoa2204705","article-title":"Trial of antisense oligonucleotide Tofersen for SOD1 ALS","volume":"387","author":"Miller","year":"2022","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.ebiom.2024.105322_bib114","series-title":"FDA approves treatment of amyotrophic lateral sclerosis associated with a mutation in the SOD1 gene","year":"2024"},{"key":"10.1016\/j.ebiom.2024.105322_bib115","series-title":"FDA grants accelerated approval for Alzheimer's disease treatment","year":"2023"},{"issue":"12","key":"10.1016\/j.ebiom.2024.105322_bib116","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1093\/brain\/awx243","article-title":"Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer's disease","volume":"140","author":"Bejanin","year":"2017","journal-title":"Brain"},{"issue":"5","key":"10.1016\/j.ebiom.2024.105322_bib117","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/NEN.0b013e31825018f7","article-title":"Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature","volume":"71","author":"Nelson","year":"2012","journal-title":"J\u00a0Neuropathol Exp Neurol"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib118","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol"},{"issue":"4","key":"10.1016\/j.ebiom.2024.105322_bib119","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.3233\/JAD-150448","article-title":"Changes in brain volume with bapineuzumab in mild to moderate Alzheimer's disease","volume":"49","author":"Novak","year":"2016","journal-title":"J\u00a0Alzheimers Dis"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib120","article-title":"Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration","volume":"13","author":"Ashton","year":"2021","journal-title":"Alzheimers Dement (Amst)"},{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib121","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1002\/alz.13518","article-title":"Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals","volume":"20","author":"Brum","year":"2024","journal-title":"Alzheimers Dement"},{"issue":"1","key":"10.1016\/j.ebiom.2024.105322_bib122","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1001\/jamaneurol.2021.4161","article-title":"Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating Aducanumab in patients with early alzheimer disease","volume":"79","author":"Salloway","year":"2022","journal-title":"JAMA Neurol"},{"issue":"11","key":"10.1016\/j.ebiom.2024.105322_bib123","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1093\/brain\/awad188","article-title":"Amyloid-related imaging abnormalities (ARIA): radiological, biological and clinical characteristics","volume":"146","author":"Hampel","year":"2023","journal-title":"Brain"},{"issue":"3","key":"10.1016\/j.ebiom.2024.105322_bib124","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1001\/jamaneurol.2021.5205","article-title":"Amyloid-related imaging abnormalities and \u03b2-amyloid-targeting antibodies: a Systematic review","volume":"79","author":"Filippi","year":"2022","journal-title":"JAMA Neurol"},{"issue":"2","key":"10.1016\/j.ebiom.2024.105322_bib125","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1001\/jamaneurol.2019.3988","article-title":"Efficacy and safety of lanabecestat for treatment of early and mild alzheimer disease: the AMARANTH and DAYBREAK-ALZ randomized clinical trials","volume":"77","author":"Wessels","year":"2020","journal-title":"JAMA Neurol"},{"issue":"3","key":"10.1016\/j.ebiom.2024.105322_bib126","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1001\/jamaneurol.2020.4857","article-title":"Findings of efficacy, safety, and biomarker outcomes of atabecestat in preclinical alzheimer disease: a truncated randomized phase 2b\/3 clinical trial","volume":"78","author":"Sperling","year":"2021","journal-title":"JAMA Neurol"}],"container-title":["eBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S235239642400358X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S235239642400358X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T13:29:16Z","timestamp":1729690156000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S235239642400358X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":126,"alternative-id":["S235239642400358X"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2024.105322","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Insights into the use of biomarkers in clinical trials in Alzheimer's disease","name":"articletitle","label":"Article Title"},{"value":"eBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2024.105322","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"105322"}}