Equivalence of plasma and serum for clinical measurement of p-tau217: comparative analyses of four blood-based assays DOI
Yijun Chen, Adelin Albert, Anuradha Sehrawat

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Phosphorylated tau (p-tau) 217 is a promising blood biomarker for Alzheimer's disease (AD). However, most p-tau217 assays have been validated solely in ethylenediaminetetraacetic acid (EDTA) plasma, leaving the clinical applicability of serum largely unexplored despite being preferred matrix many laboratories. To address this gap, we compared concentrations and diagnostic performances matched plasma samples using four research-use-only assays, including three from commercial sources i.e., Lumipulse, ALZpath, NULISA, one University Pittsburgh. Paired were processed same venipuncture collection assessed with following manufacturer-recommended procedures two research cohorts (N=84). Plasma levels varied across assays; Pittsburgh, NULISA methods showed significantly lower (p<0.0001), while Lumipulse higher or non-significant differences serum. Yet, strong correlations (rho >0.8) observed between pairs. Both demonstrated classification accuracies to differentiate AD normal controls, high AUC (up 0.963) all methods. The exception was Pittsburgh assay, where had superior than (plasma: 0.912, serum: 0.844). rest equivalent both matrices. Serum performs equivalently as assays. can therefore be used place assessment purposes.

Language: Английский

Cut‐points and gray zones: The challenges of integrating Alzheimer's disease plasma biomarkers into clinical practice DOI Creative Commons
Jemma Hazan, Kathy Liu, Jeremy D. Isaacs

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Abstract Plasma biomarkers for Alzheimer's disease (AD), such as plasma phosphorylated (p)‐tau217, offer a more accessible means of testing the presence AD pathology compared to cerebrospinal fluid (CSF) or positron emission tomography (PET) methods. They can support diagnostic assessment and determine patient eligibility treatment with amyloid beta–lowering drugs in community settings where access CSF examination amyloid‐PET are limited. However, there important challenges associated interpreting integrating biomarker results clinical practice. This article explores different approaches secondary care, potential sources uncertainty, considerations their application. Highlights tau‐217 (p‐tau217) promising, alternative detecting pathology, especially limited resources. Clinical integration presents challenges, particularly results. includes uncertainties around intermediate role management. Clear frameworks guidelines essential optimize use biomarkers, supported by further research education ensure effective application

Language: Английский

Citations

1
Blood biomarkers differentiate AD‐related versus non‐AD‐related cognitive deficits DOI Creative Commons
Kelsey R. Sewell, Lauren E. Oberlin, Thomas K. Karikari

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Abstract INTRODUCTION The utility of blood‐based biomarkers for discriminating Alzheimer's disease (AD)‐related versus non‐AD‐related cognitive deficits in preclinical populations remains poorly understood. Here, we tested the capability blood markers to detect and discriminate variation performance across multiple domains a cognitively unimpaired sample. METHODS Participants ( n = 648, aged 69.9 ± 3.8, 71% female) underwent comprehensive assessment assays plasma‐based amyloid beta (Aβ)1‐42/1‐40 by mass spectrometry, phosphorylated tau (p‐tau) 181 217, p‐tau217/Aβ1‐42, glial fibrillary acidic protein (GFAP), neurofilament light (NfL). RESULTS Greater p‐tau217 was exclusively associated with poorer episodic memory (β −0.11, SE 0.04, p .003), remained so after covarying NfL. Higher NfL non‐specifically range p‐tau217. DISCUSSION Blood‐based may differentiate AD‐related deficits. This characterization will be important early intervention monitoring AD. Highlights There is heterogeneity causes decline aging. help characterize these causes. Elevated memory. cognition broad domains. Blood AD‐

Language: Английский

Citations

0
Differences in Alzheimer's disease blood biomarker stability: Implications for the use of tau/amyloid ratios DOI Creative Commons
Daniel Figdore,

Bethany J. Schuder,

Susan Ashrafzadeh‐Kian

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(4)

Published: April 1, 2025

We compare the stability of phosphorylated tau (p-tau)217, amyloid beta (Aβ)42, Aβ40, Aβ42/40, and p-tau217/Aβ42 at different storage temperatures. Ten ethylenediaminetetraacetic acid-plasma sample aliquots stored frozen, refrigerated, ambient temperatures were tested various timepoints up to 30 days. The mean percent change from baseline was calculated. Aβ42 Aβ40 concentrations decreased by >15% after 6 hours temperature 24 while p-tau217 remained stable over 72 with < 10% deviation either temperature. Aβ42/40 ratio relatively constant as each analyte concentration concurrently, deviated time. All biomarkers days frozen. Differences in may lead altered results if samples are not handled properly during pre-analytical testing phase. Ideally, should be frozen promptly sent laboratory Plasma assessed. P-tau217 stable, but started decreasing differences led falsely increased ratios. Increases > 15% seen or 4°C.

Language: Английский

Citations

0
Diagnostic performance of plasma p-tau217 in a memory clinic cohort using the Lumipulse automated platform DOI Creative Commons
Francisco Martínez‐Dubarbie, Armando Ruiz, Sara López‐García

et al.

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 27, 2025

Plasma biomarkers for Alzheimer's disease (AD) are a promising tool accessible and accurate biological diagnostics. However, data in clinical practice needed to better understand their diagnostic prognostic ability memory unit patients. We analyzed plasma phosphorylated tau at threonine 217 (p-tau217) neuroflament light chain (NfL) levels AD cerebrospinal fluid (CSF) group of 493 subjects using the Lumipulse G600II platform. The sample includes 340 patients from our (142 dementia, 186 mild cognitive impairment, 12 with subjective complaints) 153 cognitively unimpaired volunteers. have correlated CSF biomarkers; we biomarker as function diagnosis, status amyloid status. also studied p-tau217 discriminate between amyloid-positive -negative according receiver operating characteristic curves. significantly Aβ42/Aβ40 (Rho = -0.75; p-value < 0.001), p-tau181 (r 0.66; t-tau 0.59; 0.001). NfL 0.48; By showed be higher than healthy controls (difference 0.63 pg/ml; FTD 0.60 nondegenerative dementias 0.61 an area under curve 0.95 A + A- (95%CI 0.93–0.97). shows excellent results detecting pathology brain level setting AUC 0.95. It is highly specific marker increases progressively along continuum. Using initial cut-offs sensitivities specificities 95 or 97.5% could save 57.4–84.8% LP/PETs accuracies 95–97%. different stages.

Language: Английский

Citations

0
Assessing diagnostic performance of plasma biomarkers in Alzheimer’s disease versus cognitively unimpaired individuals: P-tau217 emerges as the optimal marker in Chinese cohorts DOI Creative Commons

Shinan Wang,

Dequan Liu, Haiyan Li

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: March 26, 2025

Introduction The Simoa platform is recognized as a highly sensitive tool for detecting blood-based biomarkers of Alzheimer’s disease (AD). It extensively utilized in the diagnosis and identification AD, with accuracy emerging pivotal metric assessing assay performance, gradually gaining acceptance application. primary objective this study was to assess diagnostic efficacy multiple AD using platform. ultimate goal identify optimal further investigate their practical application value Chinese population. Methods comprised two cohorts: cohort I consisted 151 healthy controls 90 patients, while II sourced from population cohort, encompassing 123 126 utilizing publicly available data. All patients underwent plasma biomarker concentration measurements specificity, sensitivity, these were compared evaluate efficacy. Results findings revealed that P-tau217 exhibited excellent performance differentiating controls, sensitivity 95.0%, specificity 96.0%, 95.7% diagnosis. Conversely, other indicators, including Aβ42, Aβ42/40, T-tau/Aβ42, P-tau217/Aβ42 P-tau181, demonstrated some but fell short meeting criteria. Discussion stands out effective distinguishing CUC, exhibiting extensive clinical potential presents promising array prospects

Language: Английский

Citations

0
Plasma Biomarkers for Early Detection and Staging of Alzheimer’s Disease: A Cross-Sectional Study in a Japanese Cohort DOI Creative Commons

Masahito Kubota,

Shogyoku Bun, Keisuke Takahata

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Background Plasma biomarkers offer a promising alternative to amyloid beta (Aβ) PET or cerebrospinal fluid (CSF) for diagnosing Alzheimer’s disease (AD). This cross-sectional study assessed the utility of multiple plasma in Japanese cohort, including healthy controls (HC), individuals on AD continuum, and those with non-AD cognitive impairment. Methods Participants were classified using Aβ imaging neuropsychological tests into HC, continuum (preclinical [preAD], mild impairment [AD-MCI], dementia [AD-D]), groups. We conducted ROC analyses predict status, correlation Centiloid (CL) values scores, biomarker comparisons across stages. included Aβ42/40, phosphorylated tau (p-tau181, p-tau217), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), individually combination. Aβ42/40 was measured via High-Sensitivity Chemiluminescence Enzyme Immunoassay (HISCL), while all other Single Molecule Array (Simoa) platform. Results A total 69 13 preAD, 37 AD-MCI, 44 AD-D, 80 participants analyzed. AUCs predicting status 0.931 (Aβ42/40), 0.924 (p-tau217), 0.944 (p-tau217/Aβ42). In cognitively normal group, 0.968 0.958 0.979 (p-tau217/Aβ42), impaired they 0.907 0.890 0.921 Among HC participants, CL correlations 0.75 0.81 0.83 All correlated strongly Logical Memory scores. levels declined sharply from transitioning at threshold 19.3, positivity 32.9. P-tau217 exhibited linear increase progression. Conclusions biomarkers, p-tau217, particularly their ratio show strong potential as alternatives diagnosis. HISCL-based detects accumulation earlier (CL = 20) than visual reading 32.9), underscoring its an early diagnostic marker. consistently tracks progression, reinforcing value staging. Longitudinal validation these findings is needed.

Language: Английский

Citations

0
Equivalence of plasma and serum for clinical measurement of p-tau217: comparative analyses of four blood-based assays DOI
Yijun Chen, Adelin Albert, Anuradha Sehrawat

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Phosphorylated tau (p-tau) 217 is a promising blood biomarker for Alzheimer's disease (AD). However, most p-tau217 assays have been validated solely in ethylenediaminetetraacetic acid (EDTA) plasma, leaving the clinical applicability of serum largely unexplored despite being preferred matrix many laboratories. To address this gap, we compared concentrations and diagnostic performances matched plasma samples using four research-use-only assays, including three from commercial sources i.e., Lumipulse, ALZpath, NULISA, one University Pittsburgh. Paired were processed same venipuncture collection assessed with following manufacturer-recommended procedures two research cohorts (N=84). Plasma levels varied across assays; Pittsburgh, NULISA methods showed significantly lower (p<0.0001), while Lumipulse higher or non-significant differences serum. Yet, strong correlations (rho >0.8) observed between pairs. Both demonstrated classification accuracies to differentiate AD normal controls, high AUC (up 0.963) all methods. The exception was Pittsburgh assay, where had superior than (plasma: 0.912, serum: 0.844). rest equivalent both matrices. Serum performs equivalently as assays. can therefore be used place assessment purposes.

Language: Английский

Citations

0