The Amyloid-β Oligomer Count in Cerebrospinal Fluid is a Biomarker for Alzheimer's Disease

Wang-Dietrich, Lei; Funke, Susanne Aileen; Kühbach, Katja; Wang, Kun; Besmehn, Astrid; Willbold, Sabine; Cinar, Yeliz; Bannach, Oliver; Birkmann, Eva; Willbold, Dieter

doi:10.3233/jad-122047

Cited by 63 publications

(41 citation statements)

References 46 publications

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“…In 2013, the A␤ aggregate content in CSF samples of 14 AD patients and 12 age-matched controls was determined. The AD group had a significantly higher level of A␤ aggregates and the sFIDA readout correlated negatively to the MMSE score [50].…”

Section: Methods For Detection Of Single A␤ Oligomers In Csfmentioning

confidence: 99%

“…In addition, a part of total A␤ in the preparation will be removed by centrifugation, chromatography, or similar methods, leading to wrong estimation of the oligomer concentration in the standard preparation. Oligomers for standardization and determination of detection limit were often prepared from synthetic monomeric A␤ after hexafluoro-2-propanol (HFIP) treatment, dissolution in dimethyl sulfoxide (DMSO), and further dilution in phenol red free F12 culture medium [30,32], HFIP pretreatment and incubation, or HFIP pretreatment and size exclusion chromatography [50]. For direct comparison of standard generation procedures, see Tables 1-3.…”

Section: Discussion and Outlookmentioning

confidence: 99%

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Methods for the Specific Detection and Quantitation of Amyloid-β Oligomers in Cerebrospinal Fluid

Schuster

Funke

2016

JAD

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Abstract. Protein misfolding and aggregation are fundamental features of the majority of neurodegenerative diseases, like Alzheimer's disease (AD), Parkinson's disease, frontotemporal dementia, and prion diseases. Proteinaceous deposits in the brain of the patient, e.g., amyloid plaques consisting of the amyloid-␤ (A␤) peptide and tangles composed of tau protein, are the hallmarks of AD. Soluble oligomers of A␤ and tau play a fundamental role in disease progression, and specific detection and quantification of the respective oligomeric proteins in cerebrospinal fluid may provide presymptomatically detectable biomarkers, paving the way for early diagnosis or even prognosis. Several studies on the development of techniques for the specific detection of A␤ oligomers were published, but some of the existing tools do not yet seem to be satisfactory, and the study results are contradicting. The detection of oligomers is challenging due to their polymorphous and unstable nature, their low concentration, and the presence of competing proteins and A␤ monomers in body fluids. Here, we present an overview of the current state of the development of methods for A␤ oligomer specific detection and quantitation. The methods are divided in the three subgroups: (i) enzyme linked immunosorbent assays (ELISA), (ii) methods for single oligomer detection, and (iii) others, which are mainly biosensor based methods.

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Section: Methods For Detection Of Single A␤ Oligomers In Csfmentioning

confidence: 99%

Section: Discussion and Outlookmentioning

confidence: 99%

Methods for the Specific Detection and Quantitation of Amyloid-β Oligomers in Cerebrospinal Fluid

Schuster

Funke

2016

JAD

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“…SO Aβ has been shown to affect brain structures [5] and impair synaptic plasticity and formation as well as learning and memory when injected into animal brains [6][7][8][9]. In addition, SO Aβ is strongly correlated with the pathogenesis of dementia [10]. Therefore, targeting SO Aβ may serve as a valuable and promising therapeutic strategy for AD.…”

Section: Introductionmentioning

confidence: 98%

Bis(propyl)-cognitin Prevents β-amyloid-induced Memory Deficits as Well as Synaptic Formation and Plasticity Impairments via the Activation of PI3-K Pathway

Jiang

Huang

et al. 2015

Mol Neurobiol

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Bis(propyl)-cognitin (B3C), derived from tacrine linked with three methylene (-CH2-) groups, is a dimerized molecule interacting multiple targets. During the past several years, it has been reported as a promising therapeutic drug for Alzheimer's disease (AD) and other neurodegenerative disorders. However, the therapeutic mechanism of B3C for AD needs further demonstration. Based on a combination of behavioral tests, electrophysiological technique, immunocytochemistry, and live cell imaging, we studied the effects and the underlying mechanism of B3C on the impairments of cognitive function, synapse formation, and synaptic plasticity induced by soluble amyloid-β protein (Aβ) oligomers. Our study showed that spatial learning and memory in a Morris water maze task and recognition memory in a novel object recognition task were significantly decreased in the AD model mice created by hippocampal injection of Aβ. Chronic administration of B3C for 21 days prevented the memory impairments of the AD model mice in a dose-dependent manner. Live cell imaging study showed that 2-h pretreatment of B3C prevented the decrease in the number of filopodia and synapses induced by Aβ (0.5 μM) in a dose-dependent manner. Besides, electrophysiological recording data showed that the inhibition of long-term potentiation (LTP) induced by Aβ1-42 oligomers in the dentate gyrus (DG) of hippocampus was prevented by B3C in a dose-dependent manner. Furthermore, we found that the neuroprotective effect of B3C against Aβ-oligomer-induced impairments of synaptic formation and plasticity could be partially blocked by a specific phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 (50 μM). Therefore, these results indicate that B3C can prevent Aβ-oligomer-induced cognitive deficits, synaptic formation impairments, and synaptic plasticity impairments in a concentration-dependent manner. These effects of B3C are partially mediated via the PI3-K pathway. This study provides novel insights into the cellular mechanisms for the protective effects of B3C on AD.

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“…[19] Multiple approaches have been published for capturing/detecting soluble aggregated forms of Aβ: Aβ oligomer specific antibodies; [20][21][22][23][24] simultaneous application of multiple Nterminal specific antibodies; [25][26][27][28] a generic aggregation-sensitive peptide, [29] and Aβ self-recognition via seeded polymerization. [30,31] Advanced detection methods have also been utilized for Aβ oligomer sensing, [32] including DNA biobarcode amplification [21], localized surface plasmon resonance [20] and electrochemical techniques.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Multivalent foldamer-based affinity assay for selective recognition of Aβ oligomers

Olajos

Bartus

Schuster

et al. 2017

Analytica Chimica Acta

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Mimicking the molecular recognition functionality of antibodies is a great challenge. Foldamers are attractive candidates because of their relatively small size and designable interaction surface. This paper describes a sandwich type enzyme-linked immunoassay with a tetravalent β-peptide foldamer helix array as capture element and enzyme labeled tracer antibodies. The assay was found to be selective to β-amyloid oligomeric species with surface features transiently present in ongoing aggregation. In optimized conditions, with special emphasis on the foldamer immobilization, a detection limit of 5 pM was achieved with a linear range of 10 -500 pM. These results suggest that protein mimetic foldamers can be useful tools in biosensors and affinity assays.

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The Amyloid-β Oligomer Count in Cerebrospinal Fluid is a Biomarker for Alzheimer's Disease

Cited by 63 publications

References 46 publications

Methods for the Specific Detection and Quantitation of Amyloid-β Oligomers in Cerebrospinal Fluid

Methods for the Specific Detection and Quantitation of Amyloid-β Oligomers in Cerebrospinal Fluid

Bis(propyl)-cognitin Prevents β-amyloid-induced Memory Deficits as Well as Synaptic Formation and Plasticity Impairments via the Activation of PI3-K Pathway

Multivalent foldamer-based affinity assay for selective recognition of Aβ oligomers

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