Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease

Thijssen, Elisabeth H.; Verberk, Inge M.W.; Vanbrabant, Jeroen; Koelewijn, Anne; Heijst, Hans; Scheltens, Philip; Flier, Wiesje Van der; Vanderstichele, Hugo; Stoops, Erik; Teunissen, Charlotte E.

doi:10.1038/s41598-021-89004-x

Cited by 56 publications

(49 citation statements)

References 33 publications

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“…Furthermore, several studies reported similar findings comparing enzyme‐linked immunosorbent assays and Simoa platforms for plasma Aβ40 and Aβ42. 7 , 14 , 15 Spearman coefficients were 0.68 and 0.71 for, respectively, Aβ40 and Aβ42, which corroborates the findings in this article for the same assays. Since completion of this study, many of the methods have undergone additional refinement and new method comparison studies are underway.…”

Section: Discussionsupporting

confidence: 90%

The global Alzheimer's Association round robin study on plasma amyloid β methods

Pannee

Shaw

Korecka

et al. 2021

Alz & Dem Diag Ass & Dis Mo

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Introduction Blood‐based assays to measure brain amyloid beta (Aβ) deposition are an attractive alternative to the cerebrospinal fluid (CSF)–based assays currently used in clinical settings. In this study, we examined different blood‐based assays to measure Aβ and how they compare among centers and assays. Methods Aliquots from 81 plasma samples were distributed to 10 participating centers. Seven immunological assays and four mass‐spectrometric methods were used to measure plasma Aβ concentrations. Results Correlations were weak for Aβ42 while Aβ40 correlations were stronger. The ratio Aβ42/Aβ40 did not improve the correlations and showed weak correlations. Discussion The poor correlations for Aβ42 in plasma might have several potential explanations, such as the high levels of plasma proteins (compared to CSF), sensitivity to pre‐analytical sample handling and specificity, and cross‐reactivity of different antibodies. Different methods might also measure different pools of plasma Aβ42. We, however, hypothesize that greater correlations might be seen in future studies because many of the methods have been refined during completion of this study.

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Section: Discussionsupporting

confidence: 90%

The global Alzheimer's Association round robin study on plasma amyloid β methods

Pannee

Shaw

Korecka

et al. 2021

Alz & Dem Diag Ass & Dis Mo

Self Cite

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“…Finally, the discovery and validation of AD bloodbased biomarkers, made possible with the development of novel techniques (e.g. immunoprecipitation-mass spectrometry or the high-precision immunoassays) [23,25,[99][100][101] will offer major opportunities for screening and enrollment of potential participants for primary and secondary prevention trials, reducing trial duration and costs due to screen failures.…”

Section: Discussionmentioning

confidence: 99%

The informed road map to prevention of Alzheimer Disease: A call to arms

McDade,

Llibre-Guerra,

Holtzman

et al. 2021

Mol Neurodegeneration

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Alzheimer disease (AD) prevention trials hold the promise to delay or prevent cognitive decline and dementia onset by intervening before significant neuronal damage occurs. In recent years, the first AD prevention trials have launched and are yielding important findings on the biology of targeting asymptomatic AD pathology. However, there are limitations that impact the design of these prevention trials, including the translation of animal models that recapitulate key stages and multiple pathological aspects of the human disease, missing target validation in asymptomatic disease, uncertain causality of the association of pathophysiologic changes with cognitive and clinical symptoms, and limited biomarker validation for novel targets. The field is accelerating advancements in key areas including the development of highly specific and quantitative biomarker measures for AD pathology, increasing our understanding of the course and relationship of amyloid and tau pathology in asymptomatic through symptomatic stages, and the development of powerful interventions that can slow or reverse AD amyloid pathology. We review the current status of prevention trials and propose key areas of needed research as a call to basic and translational scientists to accelerate AD prevention. Specifically, we review (1) sporadic and dominantly inherited primary and secondary AD prevention trials, (2) proposed targets, mechanisms, and drugs including the amyloid, tau, and inflammatory pathways and combination treatments, (3) the need for more appropriate prevention animal models and experiments, and (4) biomarkers and outcome measures needed to design human asymptomatic prevention trials. We conclude with actions needed to effectively move prevention targets and trials forward.

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“…However, as far as we know, blood-based Aβ assay technologies using ELISA and mass spectrometry demonstrate LoD values in the hundreds of pg/mL ( Sehlin et al, 2010 ; Oeckl and Otto, 2019 ). In addition, recent studies related to blood-based AD diagnosis have reported that digital ELISA technology, or the single molecule assay (SIMOA), can detect specific N-terminal Aβ peptides in plasma with high accuracy ( De Meyer et al, 2020 ; Thijssen et al, 2021 ). Immunomagnetic reduction (IMR) technology has also been introduced as a promising blood-based biomarker platform to diagnose AD at early stages ( Yang et al, 2017 ; Lue et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Association Between Plasma Amyloid-β and Neuropsychological Performance in Patients With Cognitive Decline

Yun

Kim

et al. 2021

Front. Aging Neurosci.

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Objective: To investigate the association between plasma amyloid-β (Aβ) levels and neuropsychological performance in patients with cognitive decline using a highly sensitive nano-biosensing platform.Methods: We prospectively recruited 44 patients with cognitive decline who underwent plasma Aβ analysis, amyloid positron emission tomography (PET) scanning, and detailed neuropsychological tests. Patients were classified into a normal control (NC, n = 25) or Alzheimer’s disease (AD, n = 19) group based on amyloid PET positivity. Multiple linear regression was performed to determine whether plasma Aβ (Aβ40, Aβ42, and Aβ42/40) levels were associated with neuropsychological test results.Results: The plasma levels of Aβ42/40 were significantly different between the NC and AD groups and were the best predictor of amyloid PET positivity by receiver operating characteristic curve analysis [area under the curve of 0.952 (95% confidence interval, 0.892–1.000)]. Although there were significant differences in the neuropsychological performance of cognitive domains (language, visuospatial, verbal/visual memory, and frontal/executive functions) between the NC and AD groups, higher levels of plasma Aβ42/40 were negatively correlated only with verbal and visual memory performance.Conclusion: Our results demonstrated that plasma Aβ analysis using a nano-biosensing platform could be a useful tool for diagnosing AD and assessing memory performance in patients with cognitive decline.

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Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease

Cited by 56 publications

References 33 publications

The global Alzheimer's Association round robin study on plasma amyloid β methods

The global Alzheimer's Association round robin study on plasma amyloid β methods

The informed road map to prevention of Alzheimer Disease: A call to arms

Association Between Plasma Amyloid-β and Neuropsychological Performance in Patients With Cognitive Decline

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