Detection of amyloid β oligomers toward early diagnosis of Alzheimer's disease

Hwang, Soyoon; Chan, Hon Kit; Sorci, Mirco; Deventer, James A. Van; Wittrup, Dane; Belfort, Georges; Walt, David R.

doi:10.1016/j.ab.2018.09.011

Cited by 31 publications

(23 citation statements)

References 33 publications

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“…However, in their work, the potential of Aβ oligomerization in CSF or plasma as a biomarker was not fully addressed. Recently, a detection method for Aβ oligomers using single molecule arrays (Simoa) as a highly sensitive platform was reported using the same anti-Aβ N-terminal antibody (bapineuzumab), both for antigen capture and detection [51]. However, this strategy cannot exclude the possibility of detecting mature fibrils, resulting in lower specificity for Aβ oligomers [52].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Toxic Amyloid β42 Oligomers in Rat Primary Cerebral Cortex Cells and Human iPS-derived Neurons Treated with 10-Me-Aplog-1, a New PKC Activator

Murakami

Yoshimura

Nakagawa

et al. 2020

IJMS

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Amyloid β42 (Aβ42), a causative agent of Alzheimer's disease (AD), is derived extracellularly from Aβ precursor protein (APP) following the latter's cleavage by β-secretase, but not α-secretase. Protein kinase Cα (PKCα) activation is known to increase α-secretase activity, thereby suppressing Aβ production. Since Aβ42 oligomer formation causes potent neurotoxicity, APP modulation by PKC ligands is a promising strategy for AD treatment. Although bryostatin-1 (bryo-1) is a leading compound for this strategy, its limited natural availability and the difficulty of its total synthesis impedes further research. To address this limitation, Irie and colleagues have developed a new PKC activator with few side effects, 10-Me-Aplog-1, (1), which decreased Aβ42 in the conditioned medium of rat primary cerebral cortex cells. These results are associated with increased α-secretase but not PKCε-dependent Aβ-degrading enzyme. The amount of neuronal embryonic lethal abnormal vision (nELAV), a known β-secretase stabilizer, was reduced by treatment with 1. Notably, 1 prevented the formation of intracellular toxic oligomers. Furthermore, 1 suppressed toxic oligomerization within human iPS-derived neurons such as bryo-1. Given that 1 was not neurotoxic toward either cell line, these findings suggest that 1 is a potential drug lead for AD therapy. be more complex, given the recent discovery of APP proteolysis by ηand δ-secretases, for example, in [3]. The ability of Aβ42 to aggregate and exhibit neurotoxicity is higher than that of Aβ40 despite the lower in vivo amounts of Aβ42 [4]. Aβ42 oligomer formation causes synaptic dysfunction and neuronal death in AD pathology, whereas the contribution of end-stage mature fibrils of Aβ42 to AD is lower than that of oligomers [5]. Higher-order toxic oligomers that show potent synaptotoxicity and neurotoxicity have been reported, such as protofibrils (PFs), Aβ-derived diffusible ligands, and amylospheroids [6]. Therefore, suppressing toxic oligomerization of Aβ42 is a favorable strategy for developing AD therapies. This suppression can also be achieved by simultaneously decreasing Aβ production while inducing Aβ degradation.Protein kinase C (PKC) is a family of serine/threonine kinases that plays a pivotal role in various biological events such as signal transduction, proliferation, and apoptosis mediated by the second messenger 1,2-diacyl-sn-glycerol [7]. The PKC family, which contains at least 10 isozymes, is divided into three groups, namely conventional (α, βI, βII, and γ), novel (δ, ε, η, and θ), and atypical (µ, ξ, and ι) [7]. PKC activity is related to memory formation and learning [8], while PKC downregulation may induce cognitive impairment and memory loss in AD [9]. Regarding Aβ-driven molecular events, PKCα reportedly upregulates α-secretase activity either directly or indirectly through the mitogen-activated protein kinase (MAPK) pathway [10]. PKCα activation in a mouse model of AD has beneficial effects on AD pathology, including the disruption of Aβ production and reduction of toxi...

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Section: Discussionmentioning

confidence: 99%

Evaluation of Toxic Amyloid β42 Oligomers in Rat Primary Cerebral Cortex Cells and Human iPS-derived Neurons Treated with 10-Me-Aplog-1, a New PKC Activator

Murakami

Yoshimura

Nakagawa

et al. 2020

IJMS

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“…Nowadays, the priority in design and development of QCM analytical platforms is given to naturally occurring compounds, since they are excellent receptors with superior selectivity for the target analytes [ 28 ]. The data acquired from liquid analysis require assessment of potential contributions from surface microporosity changes, which can be solved using a quartz crystal microbalance with dissipation monitoring (QCM-D), preferred in the measurement of molecular aggregation [ 29 , 30 ]. QCM-D technology enables measurement of not only frequency but also the dissipated energy of the oscillating crystal, which makes it a promising tool for investigation of the adsorption of biomolecules that have a tendency to form films with high viscoelasticity [ 31 ].…”

Section: Qcm Technology Basicsmentioning

confidence: 99%

Application of QCM in Peptide and Protein-Based Drug Product Development

2020

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AT-cut quartz crystals vibrating in the thickness-shear mode (TSM), especially quartz crystal resonators (QCRs), are well known as very efficient mass sensitive systems because of their sensitivity, accuracy, and biofunctionalization capacity. They are highly reliable in the measurement of the mass of deposited samples, in both gas and liquid matrices. Moreover, they offer real-time monitoring, as well as relatively low production and operation costs. These features make mass sensitive systems applicable in a wide range of different applications, including studies on protein and peptide primary packaging, formulation, and drug product manufacturing process development. This review summarizes the information on some particular implementations of quartz crystal microbalance (QCM) instruments in protein and peptide drug product development as well as their future prospects.

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“…This can be attributed to achievement and recognition of immunoassays as a popular and efficient method for Aβ peptides quantification, and translation of scientific outcomes for this purpose into industrial products (i. e. commercial enzyme‐linked immunosorbent assay (ELISA) kits for Aβ peptides detection). Among the methods for tracing Aβ peptides in CSF, [7,13–15] immunoassays, notably ELISA, [2,16,17] single molecule array (SiMoA) [18,19] and multi‐analyte profiling assay (Luminex xMAP) [20] have been up to now the most practiced ones in clinical routine. Some considerations (if not drawbacks) for conventional immunoassays should be nevertheless considered (see [21,22] ), notably a lack of antibodies specific to all Aβ peptides of interest (other than those specific to the well‐studied Aβ 1–40 and 1–42), and cross reactions of different truncated Aβ peptides with the antibodies employed.…”

Section: A Glance At the Developments For Aβ Peptides Analysis Detectionmentioning

confidence: 99%

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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Detection of amyloid β oligomers toward early diagnosis of Alzheimer's disease

Cited by 31 publications

References 33 publications

Evaluation of Toxic Amyloid β42 Oligomers in Rat Primary Cerebral Cortex Cells and Human iPS-derived Neurons Treated with 10-Me-Aplog-1, a New PKC Activator

Evaluation of Toxic Amyloid β42 Oligomers in Rat Primary Cerebral Cortex Cells and Human iPS-derived Neurons Treated with 10-Me-Aplog-1, a New PKC Activator

Application of QCM in Peptide and Protein-Based Drug Product Development

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

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