{"id":"https://openalex.org/W7213916626","doi":"https://doi.org/10.64898/2026.09.18.26363412","title":"Physiological variability in key Alzheimer\u2019s biomarkers in amyloid-positive clinical trial cohorts and the mechanistic basis of biomarker ratios","display_name":"Physiological variability in key Alzheimer\u2019s biomarkers in amyloid-positive clinical trial cohorts and the mechanistic basis of biomarker ratios","publication_year":2026,"publication_date":"2026-09-21","ids":{"openalex":"https://openalex.org/W7213916626","doi":"https://doi.org/10.64898/2026.09.18.26363412"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.18.26363412","doi":"https://doi.org/10.64898/2026.09.18.26363412","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.18.26363412","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/21/2026.09.18.26363412.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/21/2026.09.18.26363412.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5000356575","display_name":"Eve Tasiudi","orcid":"https://orcid.org/0000-0002-5425-7675","observed_orcids":["https://orcid.org/0000-0002-5425-7675"]},"institutions":[{"id":"https://openalex.org/I118019719","display_name":"F. Hoffmann-La Roche AG","ror":"https://ror.org/00by1q217","country_code":"CH","type":"company","lineage":["https://openalex.org/I118019719"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Eve Tasiudi","raw_affiliation_strings":["Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland","institution_ids":["https://openalex.org/I118019719"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006993893","display_name":"David J. Hawellek","orcid":"https://orcid.org/0000-0002-2529-3351","observed_orcids":["https://orcid.org/0000-0002-2529-3351"]},"institutions":[{"id":"https://openalex.org/I118019719","display_name":"F. Hoffmann-La Roche AG","ror":"https://ror.org/00by1q217","country_code":"CH","type":"company","lineage":["https://openalex.org/I118019719"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"David Hawellek","raw_affiliation_strings":["Neuroscience and Rare Diseases, Roche Pharmaceutical Research and Early Development (pRED), F. Hoffmann La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neuroscience and Rare Diseases, Roche Pharmaceutical Research and Early Development (pRED), F. Hoffmann La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland","institution_ids":["https://openalex.org/I118019719"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5044315864","display_name":"Eduardo A. Aponte","orcid":"https://orcid.org/0000-0001-8287-194X","observed_orcids":["https://orcid.org/0000-0001-8287-194X","https://orcid.org/0009-0001-7978-4594"]},"institutions":[{"id":"https://openalex.org/I118019719","display_name":"F. Hoffmann-La Roche AG","ror":"https://ror.org/00by1q217","country_code":"CH","type":"company","lineage":["https://openalex.org/I118019719"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Eduardo Aponte","raw_affiliation_strings":["Neuroscience and Rare Diseases, Roche Pharmaceutical Research and Early Development (pRED), F. Hoffmann La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neuroscience and Rare Diseases, Roche Pharmaceutical Research and Early Development (pRED), F. Hoffmann La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland","institution_ids":["https://openalex.org/I118019719"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5038670460","display_name":"Matt\u00e9o Tonietto","orcid":"https://orcid.org/0000-0001-9591-5710","observed_orcids":["https://orcid.org/0000-0001-9591-5710"]},"institutions":[{"id":"https://openalex.org/I118019719","display_name":"F. Hoffmann-La Roche AG","ror":"https://ror.org/00by1q217","country_code":"CH","type":"company","lineage":["https://openalex.org/I118019719"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Matteo Tonietto","raw_affiliation_strings":["Neuroscience and Rare Diseases, Roche Pharmaceutical Research and Early Development (pRED), F. Hoffmann La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neuroscience and Rare Diseases, Roche Pharmaceutical Research and Early Development (pRED), F. Hoffmann La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland","institution_ids":["https://openalex.org/I118019719"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034898819","display_name":"Holly D Soares","orcid":"https://orcid.org/0000-0002-6140-9841","observed_orcids":["https://orcid.org/0000-0002-6140-9841"]},"institutions":[{"id":"https://openalex.org/I118019719","display_name":"F. Hoffmann-La Roche AG","ror":"https://ror.org/00by1q217","country_code":"CH","type":"company","lineage":["https://openalex.org/I118019719"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Holly Soares","raw_affiliation_strings":["Neuroscience and Rare Diseases, Roche Pharmaceutical Research and Early Development (pRED), F. Hoffmann La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Neuroscience and Rare Diseases, Roche Pharmaceutical Research and Early Development (pRED), F. Hoffmann La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland","institution_ids":["https://openalex.org/I118019719"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5019917859","display_name":"Cheikh Diack","orcid":"https://orcid.org/0000-0002-6320-7522","observed_orcids":["https://orcid.org/0000-0002-6320-7522"]},"institutions":[{"id":"https://openalex.org/I118019719","display_name":"F. Hoffmann-La Roche AG","ror":"https://ror.org/00by1q217","country_code":"CH","type":"company","lineage":["https://openalex.org/I118019719"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Cheikh Diack","raw_affiliation_strings":["Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland","institution_ids":["https://openalex.org/I118019719"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5064387239","display_name":"Antoine Soubret","orcid":"https://orcid.org/0000-0002-7276-5366","observed_orcids":["https://orcid.org/0000-0002-7276-5366"]},"institutions":[{"id":"https://openalex.org/I118019719","display_name":"F. Hoffmann-La Roche AG","ror":"https://ror.org/00by1q217","country_code":"CH","type":"company","lineage":["https://openalex.org/I118019719"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Antoine Soubret","raw_affiliation_strings":["Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland","institution_ids":["https://openalex.org/I118019719"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5107593370","display_name":"Tony Kam\u2010Thong","orcid":"https://orcid.org/0000-0002-5300-9573","observed_orcids":["https://orcid.org/0000-0002-5300-9573"]},"institutions":[{"id":"https://openalex.org/I118019719","display_name":"F. Hoffmann-La Roche AG","ror":"https://ror.org/00by1q217","country_code":"CH","type":"company","lineage":["https://openalex.org/I118019719"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Tony Kam-Thong","raw_affiliation_strings":["Computational Sciences Center of Excellence, F. Hoffmann La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Computational Sciences Center of Excellence, F. Hoffmann La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland","institution_ids":["https://openalex.org/I118019719"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5004932556","display_name":"Benjamin Ribba","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I118019719","display_name":"F. Hoffmann-La Roche AG","ror":"https://ror.org/00by1q217","country_code":"CH","type":"company","lineage":["https://openalex.org/I118019719"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Benjamin Ribba","raw_affiliation_strings":["Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland","institution_ids":["https://openalex.org/I118019719"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5054492506","display_name":"Marcelo Boareto","orcid":"https://orcid.org/0000-0002-9915-6376","observed_orcids":["https://orcid.org/0000-0002-9915-6376"]},"institutions":[{"id":"https://openalex.org/I118019719","display_name":"F. Hoffmann-La Roche AG","ror":"https://ror.org/00by1q217","country_code":"CH","type":"company","lineage":["https://openalex.org/I118019719"]}],"countries":["CH"],"is_corresponding":true,"raw_author_name":"Marcelo Boareto","raw_affiliation_strings":["Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland"],"raw_orcid":"https://orcid.org/0000-0002-9915-6376","affiliations":[{"raw_affiliation_string":"Pharmaceutical Sciences, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland","institution_ids":["https://openalex.org/I118019719"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5054492506"],"corresponding_institution_ids":["https://openalex.org/I118019719"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.8374000191688538,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10086","display_name":"Alzheimer's disease research and treatments","score":0.8374000191688538,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10009","display_name":"Dementia and Cognitive Impairment Research","score":0.15360000729560852,"subfield":{"id":"https://openalex.org/subfields/2738","display_name":"Psychiatry and Mental health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11314","display_name":"Clinical Laboratory Practices and Quality Control","score":0.002199999988079071,"subfield":{"id":"https://openalex.org/subfields/3607","display_name":"Medical Laboratory Technology"},"field":{"id":"https://openalex.org/fields/36","display_name":"Health Professions"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/alzheimer-s-disease-biomarkers","display_name":"Alzheimer's disease biomarkers","score":0.8999999761581421},{"id":"https://openalex.org/keywords/inter-individual-variability","display_name":"interindividual variability","score":0.8159999847412109},{"id":"https://openalex.org/keywords/physiological-variability","display_name":"physiological variability","score":0.9190000295639038},{"id":"https://openalex.org/keywords/cerebrospinal-fluid","display_name":"cerebrospinal fluid","score":0.8220000267028809},{"id":"https://openalex.org/keywords/plasma-biomarkers","display_name":"plasma biomarkers","score":0.9490000009536743},{"id":"https://openalex.org/keywords/amyloid-beta","display_name":"amyloid-beta","score":0.6660000085830688},{"id":"https://openalex.org/keywords/tau-protein","display_name":"tau protein","score":0.6290000081062317},{"id":"https://openalex.org/keywords/neurofilament-light-chain","display_name":"neurofilament light chain","score":0.8450000286102295},{"id":"https://openalex.org/keywords/glial-fibrillary-acidic-protein","display_name":"glial fibrillary acidic protein","score":0.949999988079071},{"id":"https://openalex.org/keywords/strem2","display_name":"sTREM2","score":0.9800000190734863},{"id":"https://openalex.org/keywords/ykl-40","display_name":"YKL-40","score":0.996999979019165},{"id":"https://openalex.org/keywords/biomarker-kinetics","display_name":"biomarker kinetics","score":0.6240000128746033},{"id":"https://openalex.org/keywords/compartmentalization","display_name":"compartmentalization","score":0.38499999046325684}],"concepts":[{"id":"https://openalex.org/C2781197716","wikidata":"https://www.wikidata.org/wiki/Q864574","display_name":"Biomarker","level":2,"score":0.858299970626831},{"id":"https://openalex.org/C535046627","wikidata":"https://www.wikidata.org/wiki/Q30612","display_name":"Clinical trial","level":2,"score":0.621999979019165},{"id":"https://openalex.org/C124535831","wikidata":"https://www.wikidata.org/wiki/Q4915074","display_name":"Biomarker discovery","level":4,"score":0.6207000017166138},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5920000076293945},{"id":"https://openalex.org/C136886441","wikidata":"https://www.wikidata.org/wiki/Q926129","display_name":"Normalization (sociology)","level":2,"score":0.5504999756813049},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.4431999921798706},{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.4203000068664551},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.335099995136261},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.33309999108314514},{"id":"https://openalex.org/C66882249","wikidata":"https://www.wikidata.org/wiki/Q169336","display_name":"Homogeneous","level":2,"score":0.32910001277923584},{"id":"https://openalex.org/C63363279","wikidata":"https://www.wikidata.org/wiki/Q5133848","display_name":"Clinical significance","level":2,"score":0.3190000057220459},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3138999938964844},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.299699991941452},{"id":"https://openalex.org/C148482608","wikidata":"https://www.wikidata.org/wiki/Q17007018","display_name":"Clinical study design","level":3,"score":0.2685000002384186},{"id":"https://openalex.org/C168563851","wikidata":"https://www.wikidata.org/wiki/Q1436668","display_name":"Randomized controlled trial","level":2,"score":0.2628999948501587}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.18.26363412","doi":"https://doi.org/10.64898/2026.09.18.26363412","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.18.26363412","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/21/2026.09.18.26363412.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.18.26363412","doi":"https://doi.org/10.64898/2026.09.18.26363412","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.18.26363412","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/09/21/2026.09.18.26363412.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9922999739646912,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7213916626.pdf","grobid_xml":"https://content.openalex.org/works/W7213916626.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4312086030","https://openalex.org/W4414873918","https://openalex.org/W4388851280","https://openalex.org/W2789845349","https://openalex.org/W4312086767","https://openalex.org/W4406233952","https://openalex.org/W7204852629","https://openalex.org/W2130983640","https://openalex.org/W4239615608","https://openalex.org/W2989446795"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"Protein":[2],"biomarkers":[3,41,183,268,294,338],"in":[4,45,94,105,313],"cerebrospinal":[5],"fluid":[6],"(CSF)":[7],"and":[8,22,30,69,123,145,148,160,163,168,173,192,243,266,273,316,342],"plasma":[9,67,149],"have":[10],"established":[11],"themselves":[12],"as":[13,64],"essential":[14,87],"tools":[15],"for":[16,23,129,233,286,292,299,320],"the":[17,50,114,126,194,236,239,264,308,323,334],"diagnosis":[18],"of":[19,38,52,81,84,116,179,213,238,307,310,326,336],"neurological":[20],"disorders":[21],"disease":[24],"monitoring,":[25],"thanks":[26],"to":[27,48,75,88,112,119,124,135,176,219,259,332],"their":[28,34],"accuracy":[29],"clinical":[31,46,95,156,314],"validity.":[32],"Outside":[33],"original":[35],"intended":[36],"context":[37],"use,":[39],"protein":[40],"are":[42,99,290,296,346],"increasingly":[43],"used":[44,181],"trials":[47,96,157,315],"assess":[49],"effects":[51,237],"novel":[53],"therapies":[54],"on":[55],"brain":[56],"biology.":[57],"Physiological":[58],"differences":[59],"across":[60],"individuals":[61],"\u2014":[62,72],"such":[63],"CSF":[65,147],"or":[66,228],"volume":[68],"elimination":[70],"kinetics":[71],"also":[73],"contribute":[74],"biomarker":[76,91,121,137,224,261,311],"variability.":[77,203,221,279],"A":[78],"deeper":[79],"understanding":[80,306,322],"these":[82,206],"sources":[83,309],"variability":[85,178,215,232,312],"is":[86,256],"further":[89],"improve":[90,260],"interpretation,":[92],"particularly":[93],"where":[97],"populations":[98],"by":[100,226,339],"design":[101],"more":[102],"homogeneous":[103],"than":[104],"real-world":[106],"diagnostic":[107],"settings.":[108],"This":[109,329],"study":[110],"aimed":[111],"quantify":[113],"contributions":[115,170],"physiological":[117,167,172,202,220,231,271],"factors":[118],"inter-individual":[120,177,214],"variability,":[122,272],"identify":[125],"mechanistic":[127,142,284,324],"basis":[128,325],"why":[130,287,343],"ratio-based":[131,198,254,327,344],"normalization":[132,199,240,255],"can":[133,200],"lead":[134],"enhanced":[136],"performance.":[138],"Methods":[139],"Using":[140,245],"a":[141,210,283,318],"kinetic":[143],"framework":[144,319],"paired":[146],"baseline":[150],"data":[151],"from":[152],"four":[153],"Phase":[154],"III":[155],"(GRADUATE":[158],"I":[159],"II,":[161],"CREAD":[162],"CREAD2),":[164],"we":[165,248],"quantified":[166],"neurobiological":[169,174,278],"(hereafter,":[171],"variability)":[175],"commonly":[180],"AD":[182],"(A\u03b240,":[184],"A\u03b242,":[185],"p-tau181,":[186],"t-tau,":[187],"NfL,":[188],"GFAP,":[189],"sTREM2,":[190],"YKL-40),":[191],"evaluated":[193],"conditions":[195,251,281],"under":[196,252],"which":[197,253],"reduce":[201],"Results":[204],"In":[205],"amyloid-positive":[207],"clinical-trial":[208],"populations,":[209],"large":[211],"fraction":[212],"could":[216],"be":[217],"attributed":[218],"While":[222],"normalizing":[223],"values":[225],"A\u03b240":[227],"A\u03b242":[229],"reduced":[230],"some":[234,293],"biomarkers,":[235],"were":[241],"compartment-,":[242],"cohort-dependent.":[244],"our":[246,305],"framework,":[247],"identified":[249],"two":[250],"most":[257,347],"likely":[258],"performance:":[262],"(1)":[263],"target":[265],"reference":[267],"strongly":[269],"share":[270],"(2)":[274],"they":[275],"maintain":[276],"independent":[277],"These":[280,302],"provide":[282,317],"explanation":[285],"A\u03b2-based":[288],"ratios":[289],"useful":[291],"but":[295],"not":[297],"optimal":[298],"others.":[300],"Discussion":[301],"findings":[303],"advance":[304],"better":[321],"normalization.":[328],"work":[330],"aims":[331],"strengthen":[333],"utility":[335],"using":[337],"clarifying":[340],"when":[341],"approaches":[345],"informative.":[348]},"counts_by_year":[],"updated_date":"2026-11-08T12:12:28.789561","created_date":"2026-09-22T00:00:00"}
