Browsing by Author "Verberk, Inge M. W."

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    Characterization of pre-analytical sample handling effects on a panel of Alzheimer's disease–related blood-based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group
    (Wiley, 2022) Verberk, Inge M. W.; Misdorp, Els O.; Koelewijn, Jannet; Ball, Andrew J.; Blennow, Kaj; Dage, Jeffrey L.; Fandos, Noelia; Hansson, Oskar; Hirtz, Christophe; Janelidze, Shorena; Kang, Sungmin; Kirmess, Kristopher; Kindermans, Jana; Lee, Ryan; Meyer, Matthew R.; Shan, Dandan; Shaw, Leslie M.; Waligorska, Teresa; West, Tim; Zetterberg, Henrik; Edelmayer, Rebecca M.; Teunissen, Charlotte E.; Neurology, School of Medicine
    Introduction: Pre-analytical sample handling might affect the results of Alzheimer's disease blood-based biomarkers. We empirically tested variations of common blood collection and handling procedures. Methods: We created sample sets that address the effect of blood collection tube type, and of ethylene diamine tetraacetic acid plasma delayed centrifugation, centrifugation temperature, aliquot volume, delayed storage, and freeze–thawing. We measured amyloid beta (Aβ)42 and 40 peptides with six assays, and Aβ oligomerization-tendency (OAβ), amyloid precursor protein (APP)699-711, glial fibrillary acidic protein (GFAP), neurofilament light (NfL), total tau (t-tau), and phosphorylated tau181. Results: Collection tube type resulted in different values of all assessed markers. Delayed plasma centrifugation and storage affected Aβ and t-tau; t-tau was additionally affected by centrifugation temperature. The other markers were resistant to handling variations. Discussion: We constructed a standardized operating procedure for plasma handling, to facilitate introduction of blood-based biomarkers into the research and clinical settings.
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    Plasma biomarkers predict amyloid pathology in cognitively normal monozygotic twins after 10 years
    (Oxford University Press, 2023-02-04) den Braber, Anouk; Verberk, Inge M. W.; Tomassen, Jori; den Dulk, Ben; Stoops, Erik; Dage, Jeffrey L.; Collij, Lyduine E.; Barkhof, Frederik; Willemsen, Gonneke; Nivard, Michel G.; van Berckel, Bart N. M.; Scheltens, Philip; Visser, Pieter Jelle; de Geus, Eco J. C.; Teunissen, Charlotte E.; Neurology, School of Medicine
    Blood-based biomarkers could prove useful to predict Alzheimer's disease core pathologies in advance of clinical symptoms. Implementation of such biomarkers requires a solid understanding of their long-term dynamics and the contribution of confounding to their association with Alzheimer's disease pathology. Here we assess the value of plasma amyloid-β1-42/1-40, phosphorylated-tau181 and glial fibrillary acidic protein to detect early Alzheimer's disease pathology, accounting for confounding by genetic and early environmental factors. Participants were 200 monozygotic twins, aged ≥60 years with normal cognition from the european medical information framework for Alzheimer's disease study. All twins had amyloid-β status and plasma samples available at study enrolment. For 80 twins, additional plasma samples were available that had been collected approximately 10 years prior to amyloid-β status assessment. Single-molecule array assays were applied to measure amyloid-β1-42/1-40, phosphorylated-tau181 and glial fibrillary acidic protein. Predictive value of and longitudinal change in these biomarkers were assessed using receiver operating characteristic curve analysis and linear mixed models. Amyloid pathology could be predicted using blood-based biomarkers obtained at the time of amyloid status assessment (amyloid-β1-42/1-40: area under the curve = 0.65, P = 0.01; phosphorylated-tau181: area under the curve = 0.84, P < 0.001; glial fibrillary acidic protein: area under the curve = 0.74, P < 0.001), as well as using those obtained 10 years prior to amyloid status assessment (amyloid-β1-42/1-40: area under the curve = 0.69, P = 0.03; phosphorylated-tau181: area under the curve = 0.92, P < 0.001; glial fibrillary acidic protein: area under the curve = 0.84, P < 0.001). Longitudinally, amyloid-β1-42/1-40 levels decreased [β (SE) = -0.12 (0.01), P < 0.001] and phosphorylated-tau181 levels increased [β (SE) = 0.02 (0.01), P = 0.004]. Amyloid-β-positive individuals showed a steeper increase in phosphorylated-tau181 compared with amyloid-β-negative individuals [β (SE) = 0.06 (0.02), P = 0.004]. Also amyloid-β-positive individuals tended to show a steeper increase in glial fibrillary acidic protein [β (SE) = 0.04 (0.02), P = 0.07]. Within monozygotic twin pairs, those with higher plasma phosphorylated-tau181 and lower amyloid-β1-42/1-40 levels were more likely to be amyloid-β positive [β (SE) = 0.95 (0.26), P < 0.001; β (SE) = -0.28 (0.14), P < 0.05] indicating minimal contribution of confounding by genetic and early environmental factors. Our data support the use of amyloid-β1-42/1-40, phosphorylated-tau181 and glial fibrillary acidic protein as screening tools for Alzheimer's disease pathology in the normal aging population, which is of importance for enrolment of high-risk subjects in secondary, or even primary, prevention trials. Furthermore, these markers show potential as low-invasive monitoring tool of disease progression and possibly treatment effects in clinical trials.
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    The global Alzheimer's Association round robin study on plasma amyloid β methods
    (Wiley, 2021-10-14) Pannee, Josef; Shaw, Leslie M.; Korecka, Magdalena; Waligorska, Teresa; Teunissen, Charlotte E.; Stoops, Erik; Vanderstichele, Hugo M. J.; Mauroo, Kimberley; Verberk, Inge M. W.; Keshavan, Ashvini; Pesini, Pedro; Sarasa, Leticia; Pascual-Lucas, Maria; Fandos, Noelia; Allué, José-Antonio; Portelius, Erik; Andreasson, Ulf; Yoda, Ritsuko; Nakamura, Akinori; Kaneko, Naoki; Yang, Shieh-Yueh; Liu, Huei-Chun; Palme, Stefan; Bittner, Tobias; Mawuenyega, Kwasi G.; Ovod, Vitaliy; Bollinger, James; Bateman, Randall J.; Li, Yan; Dage, Jeffrey L.; Stomrud, Erik; Hansson, Oskar; Schott, Jonathan M.; Blennow, Kaj; Zetterberg, Henrik; Neurology, School of Medicine
    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.