biostudies-literatureLee EHKorea University Guro HospitalEuropean Union Joint Program for Neurodegenerative DisordersSwedish government and the County CouncilsKorea National Institute of HealthSwedish Research CouncilHjärnfonden, SwedenNational Research Foundation of KoreaSwedish Alzheimer FoundationLa Fondation Recherche AlzheimerFamiljen Rönströms StiftelseKirsten og Freddy Johansens FondMinistry of Health & Welfare and Ministry of Science and ICTAlzheimer's Association 2021 Zenith AwardMinistry of Science and ICT, South KoreaAlzheimer's AssociationSamsung Medical Centere14368https://www.ebi.ac.uk/biostudies/studies/S-EPMC11782842biostudies-literatureUnknown21(1)<h4>Introduction</h4>We aimed to investigate which factors affect plasma biomarker levels via amyloid beta (Aβ)-independent or Aβ-dependent effects and improve the predictive performance of these biomarkers for Aβ positivity on positron emission tomography (PET).<h4>Methods</h4>A total of 2935 participants underwent blood sampling for measurements of plasma Aβ42/40 ratio, phosphorylated tau 217 (p-tau217; ALZpath), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels using single-molecule array and Aβ PET. Laboratory findings were collected using a routine blood test battery.<h4>Results</h4>Aβ-independent factors included hemoglobin and estimated glomerular filtration rate (eGFR) for p-tau217 and hemoglobin, eGFR, and triiodothyronine (T₃) for GFAP and NfL. Aβ-dependent factors included apolipoprotein E genotypes, body mass index status for Aβ42/40, p-tau217, GFAP, and NfL. However, these factors exhibited negligible or modest effects on Aβ positivity on PET.<h4>Discussion</h4>Our findings highlight the importance of accurately interpreting plasma biomarkers for predicting Aβ uptake in real-world settings.<h4>Highlights</h4>We investigated factor-Alzheimer's disease plasma biomarker associations in a large Korean cohort. Hemoglobin and estimated glomerular filtration rate affect the biomarkers independently of brain amyloid beta (Aβ). Apolipoprotein E genotypes and body mass index status affect the biomarkers dependent on brain Aβ. Addition of Aβ-independent factors shows negligible effect in predicting Aβ positivity. Adjusting for Aβ-dependent factors shows a modest effect in predicting Aβ positivity.Alzheimer's & dementia : the journal of the Alzheimer's AssociationPlasma Alzheimer's disease biomarker variability: Amyloid-independent and amyloid-dependent factors.PMC11782842#AF-930351SG-23-1038904 QC#2022-00732#ALZ2022-0006#ALFGBG-715986NRF-2019R1A5A2027340ZEN-21-848495RS-2020-KH106434Artificial Intelligence Innovation Hub2024-ER1003-00#ALFGBG-965240#2017-00915#FO2017-0243#AF-994551No.O2400251RS-2022-KH127756No.RS-2021-II212068JPND2019-466-236#AF-968270#AF-939721#SMX1240561Yun JKim JPNa DLSeo SWKim HJK‐ROAD study groupJang HZetterberg HAshton NJKang SHShin DCheon BKKim YJHam HLee EHGonzalez-Ortiz FYoo HBlennow KfalsePlasma Alzheimer's disease biomarker variability: Amyloid-independent and amyloid-dependent factors.<h4>Introduction</h4>We aimed to investigate which factors affect plasma biomarker levels via amyloid beta (Aβ)-independent or Aβ-dependent effects and improve the predictive performance of these biomarkers for Aβ positivity on positron emission tomography (PET).<h4>Methods</h4>A total of 2935 participants underwent blood sampling for measurements of plasma Aβ42/40 ratio, phosphorylated tau 217 (p-tau217; ALZpath), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels using single-molecule array and Aβ PET. Laboratory findings were collected using a routine blood test battery.<h4>Results</h4>Aβ-independent factors included hemoglobin and estimated glomerular filtration rate (eGFR) for p-tau217 and hemoglobin, eGFR, and triiodothyronine (T₃) for GFAP and NfL. Aβ-dependent factors included apolipoprotein E genotypes, body mass index status for Aβ42/40, p-tau217, GFAP, and NfL. However, these factors exhibited negligible or modest effects on Aβ positivity on PET.<h4>Discussion</h4>Our findings highlight the importance of accurately interpreting plasma biomarkers for predicting Aβ uptake in real-world settings.<h4>Highlights</h4>We investigated factor-Alzheimer's disease plasma biomarker associations in a large Korean cohort. Hemoglobin and estimated glomerular filtration rate affect the biomarkers independently of brain amyloid beta (Aβ). Apolipoprotein E genotypes and body mass index status affect the biomarkers dependent on brain Aβ. Addition of Aβ-independent factors shows negligible effect in predicting Aβ positivity. Adjusting for Aβ-dependent factors shows a modest effect in predicting Aβ positivity.2025-01-01T00:00:00Z2025 Jan2025-04-04T20:57:10.949Z2025-04-04T20:57:10.949ZS-EPMC117828423953547310.1002/alz.14368