Critical Steps to be Taken into Consideration Before Quantification of β-Amyloid and Tau Isoforms in Blood can be Implemented in a Clinical Environment

Vanderstichele, Hugo; Teunissen, Charlotte E.; Vanmechelen, Eugeen

doi:10.1007/s40120-019-00166-3

Cited by 8 publications

(10 citation statements)

References 73 publications

(83 reference statements)

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“…This increased performance of the ratios has been linked to the correction for interindividual differences in total Aβ production in Aβ 1–42 /Aβ 1–40 and might result from capturing multiple AD dimensions in Aβ 1–42 /t-tau. Besides, the reduction in analytical confounding factors that typically arise in protein analyses, such as the presence of various blood cells, might also play an important role in the increased performance [ 38 ]. The lower specificity and PPV of plasma Aβ 1–42 /t-tau compared to plasma Aβ 1–42 /Aβ 1–40 in the CN subgroup but not in the aMCI subgroup might argue for the use of plasma Aβ 1–42 /Aβ 1–40 in prescreening of CN subjects, while plasma Aβ 1–42 /t-tau is a potential alternative in later AD stages.…”

Section: Discussionmentioning

confidence: 99%

Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis

et al. 2020

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Background Blood-based amyloid biomarkers may provide a non-invasive, cost-effective and scalable manner for detecting cerebral amyloidosis in early disease stages. Methods In this prospective cross-sectional study, we quantified plasma Aβ1–42/Aβ1–40 ratios with both routinely available ELISAs and novel SIMOA Amyblood assays, and provided a head-to-head comparison of their performances to detect cerebral amyloidosis in a nondemented elderly cohort (n = 199). Participants were stratified according to amyloid-PET status, and the performance of plasma Aβ1–42/Aβ1–40 to detect cerebral amyloidosis was assessed using receiver operating characteristic analysis. We additionally investigated the correlations of plasma Aβ ratios with amyloid-PET and CSF Alzheimer’s disease biomarkers, as well as platform agreement using Passing-Bablok regression and Bland-Altman analysis for both Aβ isoforms. Results ELISA and SIMOA plasma Aβ1–42/Aβ1–40 detected cerebral amyloidosis with identical accuracy (ELISA: area under curve (AUC) 0.78, 95% CI 0.72–0.84; SIMOA: AUC 0.79, 95% CI 0.73–0.85), and both increased the performance of a basic demographic model including only age and APOE-ε4 genotype (p ≤ 0.02). ELISA and SIMOA had positive predictive values of respectively 41% and 36% in cognitively normal elderly and negative predictive values all exceeding 88%. Plasma Aβ1–42/Aβ1–40 correlated similarly with amyloid-PET for both platforms (Spearman ρ = − 0.32, p < 0.0001), yet correlations with CSF Aβ1–42/t-tau were stronger for ELISA (ρ = 0.41, p = 0.002) than for SIMOA (ρ = 0.29, p = 0.03). Plasma Aβ levels demonstrated poor agreement between ELISA and SIMOA with concentrations of both Aβ1–42 and Aβ1–40 measured by SIMOA consistently underestimating those measured by ELISA. Conclusions ELISA and SIMOA demonstrated equivalent performances in detecting cerebral amyloidosis through plasma Aβ1–42/Aβ1–40, both with high negative predictive values, making them equally suitable non-invasive prescreening tools for clinical trials by reducing the number of necessary PET scans for clinical trial recruitment. Trial registration EudraCT 2009-014475-45 (registered on 23 Sept 2009) and EudraCT 2013-004671-12 (registered on 20 May 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004671-12/BE).

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Section: Discussionmentioning

confidence: 99%

Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis

et al. 2020

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“…Highly sensitive plasma immunoassays for ptau181 20,21 and ptau217 22–25 published beyond our search date show various associations with AD and should be included in future updates to this systematic review. Pre‐analytical variables must also be standardized 116,117 as they have been shown to influence measurement of plasma Aβ 118 and were posited to account for differences in results between cohorts, complicating the establishment of a common cutoff value 60 …”

Section: Discussionmentioning

confidence: 99%

The search for a convenient procedure to detect one of the earliest signs of Alzheimer's disease: A systematic review of the prediction of brain amyloid status

Ashford

Veitch

Neuhaus

et al. 2021

Alzheimer's & Dementia

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Introduction Convenient, cost‐effective tests for amyloid beta (Aβ) are needed to identify those at higher risk for developing Alzheimer's disease (AD). This systematic review evaluates recent models that predict dichotomous Aβ. (PROSPERO: CRD42020144734). Methods We searched Embase and identified 73 studies from 29,581 for review. We assessed study quality using established tools, extracted information, and reported results narratively. Results We identified few high‐quality studies due to concerns about Aβ determination and analytical issues. The most promising convenient, inexpensive classifiers consist of age, apolipoprotein E genotype, cognitive measures, and/or plasma Aβ. Plasma Aβ may be sufficient if pre‐analytical variables are standardized and scalable assays developed. Some models lowered costs associated with clinical trial recruitment or clinical screening. Discussion Conclusions about models are difficult due to study heterogeneity and quality. Promising prediction models used demographic, cognitive/neuropsychological, imaging, and plasma Aβ measures. Further studies using standardized Aβ determination, and improved model validation are required.

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“…This gives potential for plasma Aβ detection as a simple and minimally invasive way for early diagnosis of AD. [10] The plasma level of Aβ 1-42 (~20 pg/mL) is considerably lower than that in CSF. [11] At the present stage, AD molecular diagnosis has nevertheless not reached the expected specificity and sensitivity (< 90 %).…”

Section: Introductionmentioning

confidence: 94%

Recent Electrokinetic and Microfluidic Strategies for Detection of Amyloid Beta Peptide Biomarkers: Towards Molecular Diagnosis of Alzheimer's Disease

Nguyen

Taverna

Smadja

et al. 2020

The Chemical Record

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Among all neurodegenerative diseases, Alzheimer's Disease (AD) is the most prevalent worldwide, with a huge burden to the society and no efficient AD treatment so far. Continued efforts have been being made towards early and powerful diagnosis of AD, in the hope for a successful set of clinical trials and subsequently AD curative treatment. Towards this aim, detection and quantification of amyloid beta (Aβ) peptides in cerebrospinal fluid (CSF) and other biofluids, which are established and validated biomarkers for AD, have drawn attention of the scientific community and industry over almost two decades. In this work, an overview on our major contributions over 15 years to develop different electrokinetic and microfluidic strategies for Aβ peptides detection and quantification is reported. Accordingly, discussions and viewpoints on instrumental and methodological developments for microscale electrophoresis, microfluidic designs and immuno‐enrichment / assays on magnetic beads in microchannels for tracing Aβ peptides in CSF are given in this review.

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Critical Steps to be Taken into Consideration Before Quantification of β-Amyloid and Tau Isoforms in Blood can be Implemented in a Clinical Environment

Cited by 8 publications

References 73 publications

Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis

Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis

The search for a convenient procedure to detect one of the earliest signs of Alzheimer's disease: A systematic review of the prediction of brain amyloid status

Recent Electrokinetic and Microfluidic Strategies for Detection of Amyloid Beta Peptide Biomarkers: Towards Molecular Diagnosis of Alzheimer's Disease

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