Performance of plasma p-tau217 for the detection of amyloid-ß positivity in a memory clinic cohort using an electrochemiluminescence immunoassay.
Alzheimers Res Ther
; 16(1): 186, 2024 Aug 19.
Article
in En
| MEDLINE
| ID: mdl-39160628
ABSTRACT
BACKGROUND:
Plasma p-tau217 has emerged as the most promising blood-based marker (BBM) for the detection of Alzheimer Disease (AD) pathology, yet few studies have evaluated plasma p-tau217 performance in memory clinic settings. We examined the performance of plasma p-tau217 for the detection of AD using a high-sensitivity immunoassay in individuals undergoing diagnostic lumbar puncture (LP).METHODS:
Paired plasma and cerebrospinal fluid (CSF) samples were analysed from the TIMC-BRAiN cohort. Amyloid (Aß) and Tau (T) pathology were classified based on established cut-offs for CSF Aß42 and CSF p-tau181 respectively. High-sensitivity electrochemiluminescence (ECL) immunoassays were performed on paired plasma/CSF samples for p-tau217, p-tau181, Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light (NfL) and total tau (t-tau). Biomarker performance was evaluated using Receiver-Operating Curve (ROC) and Area-Under-the-Curve (AUC) analysis.RESULTS:
Of 108 participants (age 69 ± 6.5 years; 54.6% female) with paired samples obtained at time of LP, 64.8% (n = 70/108) had Aß pathology detected (35 with Mild Cognitive Impairment and 35 with mild dementia). Plasma p-tau217 was over three-fold higher in Aß + (12.4 pg/mL; 7.3-19.2 pg/mL) vs. Aß- participants (3.7 pg/mL; 2.8-4.1 pg/mL; Mann-Whitney U = 230, p < 0.001). Plasma p-tau217 exhibited excellent performance for the detection of Aß pathology (AUC 0.91; 95% Confidence Interval [95% CI] 0.86-0.97)-greater than for T pathology (AUC 0.83; 95% CI 0.75-0.90; z = 1.75, p = 0.04). Plasma p-tau217 outperformed plasma p-tau181 for the detection of Aß pathology (z = 3.24, p < 0.001). Of the other BBMs, only plasma GFAP significantly differed by Aß status which significantly correlated with plasma p-tau217 in Aß + (but not in Aß-) individuals. Application of a two-point threshold at 95% and 97.5% sensitivities & specificities may have enabled avoidance of LP in 58-68% of cases.CONCLUSIONS:
Plasma p-tau217 measured using a high-sensitivity ECL immunoassay demonstrated excellent performance for detection of Aß pathology in a real-world memory clinic cohort. Moving forward, clinical use of plasma p-tau217 to detect AD pathology may substantially reduce need for confirmatory diagnostic testing for AD pathology with diagnostic LP in specialist memory services.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Biomarkers
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Amyloid beta-Peptides
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Tau Proteins
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Alzheimer Disease
Limits:
Aged
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Alzheimer's res. ther
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Alzheimer's research & therapy
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Alzheimers Res Ther
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: