biostudies-literatureBrum WSNIA NIH HHSStiftelsen för Gamla TjänarinnorNational Institutes of HealthNIH HHS1284-1297https://www.ebi.ac.uk/biostudies/studies/S-EPMC10916965biostudies-literatureUnknown20(2)<h4>Introduction</h4>Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data.<h4>Methods</h4>We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p-tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CV_I ) and between-subject (CV_G ) BV, analytical variation, and reference change values (RCV).<h4>Results</h4>Biomarkers presented considerable variability in CV_I and CV_G . Aβ42/Aβ40 had the lowest CV_I (≈ 3%) and p-tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase).<h4>Discussion</h4>BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between-subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result.Alzheimer's & dementia : the journal of the Alzheimer's AssociationBiological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals.PMC10916965R37 AG023651R01 AG072641‐02#FO2022‐0270R01 AG073267RF1 AG052525R37 AG023651‐17R01 AG075336‐01R01 AG053952RF1 AG052525-01A1R01 AG075336-01P30 AG066468R01 AG053952-05R01 AG083874P01 AG025204‐16RF1 AG052525‐01A1R01 AG073267‐02RF1 AG025516‐12A1RF1 AG025516R01 AG072641-02R01 AG072641P50 AG005133R01 AG075336P01 AG025204-16P01 AG025204R37 AG023651-17RF1 AG025516-12A1R01 AG073267-02R01 AG053952‐05Sandberg SZimmer ERCoskun ADiaz-Garzon JSimren JCarobene Adi Molfetta GZetterberg HBartlett WAJonker NAshton NJMontoliu-Gaya LBrum WSLantero-Rodriguez JCalle PFJeromin ABenedet ALAarsand AKKarikari TKBlennow KfalseBiological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals.<h4>Introduction</h4>Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data.<h4>Methods</h4>We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p-tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CV_I ) and between-subject (CV_G ) BV, analytical variation, and reference change values (RCV).<h4>Results</h4>Biomarkers presented considerable variability in CV_I and CV_G . Aβ42/Aβ40 had the lowest CV_I (≈ 3%) and p-tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase).<h4>Discussion</h4>BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between-subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result.2024-01-01T00:00:00Z2024 Feb2026-06-27T03:17:22.786Z2026-06-27T03:06:51.419ZS-EPMC109169653798523010.1002/alz.13518