Plasma Amyloid Concentration in Alzheimer’s Disease: Performance of a High-Throughput Amyloid Assay in Distinguishing Alzheimer’s Disease Cases from Controls

Feinkohl, Insa; Schipke, Carola G.; Kruppa, Jochen; Winterer, Georg; Pischon, Tobias; Peters, Oliver

doi:10.3233/jad-200046

Cited by 26 publications

(27 citation statements)

References 61 publications

(89 reference statements)

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“…3 ). Furthermore, the diagnostic accuracy of our developed kit is comparable or superior to those from other tests using well-known plasma AD biomarkers such as plasma Aβ42/40 ratio, Aβ40/42 ratio, or plasma phosphorylated-tau (p-tau) (Supplementary Table 1) [ 3 , 24 – 32 ]. First, the AUC value from Model III (0.891 with 80.0% sensitivity and 83.0% specificity; the model with ApoE covariate) was the highest rank among the models using ApoE as a covariate (1st out of 3 biomarkers).…”

Section: Discussionmentioning

confidence: 85%

Performance of the QPLEX™ Alz plus assay, a novel multiplex kit for screening cerebral amyloid deposition

Park

Jung²,

Kim³

et al. 2021

Alz Res Therapy

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Background Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by the hallmark finding of cerebral amyloid deposition. Many researchers have tried to predict the existence of cerebral amyloid deposition by using easily accessible blood plasma samples, but the effectiveness of such strategies remains controversial. Methods We developed a new multiplex kit, the QPLEX™ Alz plus assay kit, which uses proteomics-based blood biomarkers to prescreen for cerebral amyloid deposition. A total of 300 participants who underwent Pittsburgh compound B (PiB)-positron emission tomography (PET) which allows imaging of cerebral amyloid deposition were included in this study. We compared the levels of QPLEX™ biomarkers between patients who were classified as PiB-negative or PiB-positive, regardless of their cognitive function. Logistic regression analysis followed by receiver operating characteristic (ROC) curve analysis was performed. The kit accuracy was tested using a randomized sample selection method. Results The results obtained using our assay kit reached 89.1% area under curve (AUC) with 80.0% sensitivity and 83.0% specificity. Further validation of the QPLEX™ Alz plus assay kit using a randomized sample selection method showed an average accuracy of 81.5%. Conclusions Our QPLEX™ Alz plus assay kit provides preliminary evidence that it can be used as blood marker to predict cerebral amyloid deposition but independent validation is needed.

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Section: Discussionmentioning

confidence: 85%

Performance of the QPLEX™ Alz plus assay, a novel multiplex kit for screening cerebral amyloid deposition

Park

Jung²,

Kim³

et al. 2021

Alz Res Therapy

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“…The neprilysin-Amyloidβ (Aβ) was selected as the enzyme-substrate prototype as recent studies have indicate the potential role of developing recombinant neprilysin as a therapeutic candidate for treating Alzheimer's disease (AD). 2,6,8,9,16 Therapeutic development of neprilysin for use in treating AD will require establishing the optimal enzyme kinetics against AD specific Aβ peptides. 2,8,9 Although the association Aβ peptides in the progression of AD is well established, developing effective treatment will require specific and selective cleaving of a variety of Aβ peptides.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The enzyme kinetics of 5JMY and Amyloid β1-40 interactions are extensively reported in the literature and forms the basis of several commercially available kits to assess neprilysin activity. 1, 6, 8, 14–16 Hence the enzymatic cleaving of Amyloid β1-40 (at a substrate concentration of 0.625, 1.25, 2.5, 5, 10, 15 and 20 μM) was studied in presence of 5 nM concentration of recombinant neprilysin (5JMY). The resultant enzyme-substrate kinetic curve was used for modelling the kinetics of rest of the Amyloid β (4XFO, 5TPT, 3SGP, 2ROZ, 2YT1, 4YN0, 2KJ7, 1NMJ, 4DBB, 2BFI, 2ONX, Aβ1-40) and neprilysin (5JMY, 6GID, 4XBH and 6GHX) combinations.…”

Section: Methodsmentioning

confidence: 99%

Section: Enzyme Kinetics Modellingmentioning

confidence: 99%

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Modelling the efficacy of Neprilysin from various species in degrading different Amyloid-β peptides: Potential application in therapeutics of Alzheimer’s disease

Kumar

2021

Preprint

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Recombinant neprilysin due to its degradation potential against Amyloid-beta (A-beta) peptides has been looked at as a potential therapeutic candidate for treating Alzheimers disease (AD). However the enzymatic activity of neprilysin against different Aβ peptides can variable which significantly limits the therapeutic optimization. Using the molecular interaction analysis and modelling it against the known enzyme-substrate kinetics, this study developed a novel approach to predicting biosimilar enzyme-substrate kinetics. The known enzyme-substrate kinetics of human recombinant neprilysin with A-beta1-40 peptide was used as the prototype to assess the affinity and efficacy of various inter and intra-species neprilysin- A-beta peptide enzyme kinetics based on the relative molecular interaction analysis. Significant inter and intra-species variations in neprilysin- A-beta peptide enzyme kinetics was observed which further validated the need for optimizing enzyme kinetics tailored to specific substrate degradation. The novel enzyme kinetics modelling approach described in this study can be helpful in the developing of recombinant enzymes/peptides for personalised therapeutic applications.

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Comparative methods for quantifying plasma biomarkers in Alzheimer's disease: Implications for the next frontier in cerebral amyloid angiopathy diagnostics

Muir,

Ismail,

Black

et al. 2023

Alzheimer's & Dementia

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Plasma amyloid beta (Aβ) and tau are emerging as accessible biomarkers for Alzheimer's disease (AD). However, many assays exist with variable test performances, highlighting the need for a comparative assessment to identify the most valid assays for future use in AD and to apply to other settings in which the same biomarkers may be useful, namely, cerebral amyloid angiopathy (CAA). CAA is a progressive cerebrovascular disease characterized by deposition of Aβ40 and Aβ42 in cortical and leptomeningeal vessels. Novel immunotherapies for AD can induce amyloid‐related imaging abnormalities resembling CAA‐related inflammation. Few studies have evaluated plasma biomarkers in CAA. Identifying a CAA signature could facilitate diagnosis, prognosis, and a safer selection of patients with AD for emerging immunotherapies. This review evaluates studies that compare the diagnostic test performance of plasma biomarker techniques in AD and cerebrovascular and plasma biomarker profiles of CAA; it also discusses novel hypotheses and future avenues for plasma biomarker research in CAA.

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Plasma Amyloid Concentration in Alzheimer’s Disease: Performance of a High-Throughput Amyloid Assay in Distinguishing Alzheimer’s Disease Cases from Controls

Cited by 26 publications

References 61 publications

Performance of the QPLEX™ Alz plus assay, a novel multiplex kit for screening cerebral amyloid deposition

Performance of the QPLEX™ Alz plus assay, a novel multiplex kit for screening cerebral amyloid deposition

Modelling the efficacy of Neprilysin from various species in degrading different Amyloid-β peptides: Potential application in therapeutics of Alzheimer’s disease

Comparative methods for quantifying plasma biomarkers in Alzheimer's disease: Implications for the next frontier in cerebral amyloid angiopathy diagnostics

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