Aβ40 Oligomers Identified as a Potential Biomarker for the Diagnosis of Alzheimer's Disease

Gao, Carol Man; Yam, Alice; Wang, Xuemei; Magdangal, Erika; Salisbury, Cleo M.; Peretz, David; Zuckermann, Ronald N.; Connolly, Michael D.; Hansson, Oskar; Minthon, Lennart; Zetterberg, Henrik; Blennow, Kaj; Fedynyshyn, Joseph P.; Allauzen, Sophie

doi:10.1371/journal.pone.0015725

Cited by 96 publications

(82 citation statements)

References 37 publications

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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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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

View full text Add to dashboard Cite

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“…Recent studies demonstrated the presence of increased levels of Aβ oligomeric species in the CSF of AD patients when compared to controls using a broad range of methodological approaches [105][106][107][108][109][110]. Indeed, the analysis of individual Aβ oligomeric species is gaining experimental momentum due to their potential specific role in AD pathogenesis.…”

Section: Aβ Oligomersmentioning

confidence: 99%

“…Indeed, the analysis of individual Aβ oligomeric species is gaining experimental momentum due to their potential specific role in AD pathogenesis. Aβ40 oligomers levels are found to be increased in the CSF of AD patients at different disease severity stages, and a combined analysis of Aβ40 oligomers and monomeric Aβ42 greatly improved sensitivity and specificity to 95% and 90%, respectively [108]. Although the pathogenic role of Aβ40 in AD is still under discussion Aβ40 deposits have been reported both in control and AD brains [111,112].…”

Section: Aβ Oligomersmentioning

confidence: 99%

New Frontiers in Alzheimer's Disease Diagnosis

Llorens¹,

Nuhn²,

Peter³

et al. 2015

Alzheimer's Disease - Challenges for the Future

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“…Carol et al showed that, in combination with total Aβ42, Aβ40 oligomers can diagnose AD remarkably with >95% sensitivity and >90% specifi city [72] .…”

Section: Aβ40 Oligomers and Aβ42mentioning

confidence: 99%

Cerebrospinal fluid biomarkers of Alzheimer’s disease

Sui

Yang

2014

Neurosci. Bull.

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Alzheimer's disease (AD) is a fatal neurodegenerative disorder that takes about a decade to develop, making early diagnosis possible. Clinically, the diagnosis of AD is complicated, costly, and inaccurate, so it is urgent to fi nd specifi c biomarkers. Due to its multifactorial nature, a panel of biomarkers for the multiple pathologies of AD, such as cerebral amyloidogenesis, neuronal dysfunction, synapse loss, oxidative stress, and infl ammation, are most promising for accurate diagnosis. Highly sensitive and high-throughput proteomic techniques can be applied to develop a panel of novel biomarkers for AD. In this review, we discuss the metabolism and diagnostic performance of the well-established core candidate cerebrospinal fl uid (CSF) biomarkers (β-amyloid, total tau, and hyperphosphorylated tau). Meanwhile, novel promising CSF biomarkers, especially those identifi ed by proteomics, updated in the last fi ve years are also extensively discussed. Furthermore, we provide perspectives on how biomarker discovery for AD is evolving.Keywords: Alzheimer's disease; biomarker; cerebrospinal fl uid; β-amyloid; tau; proteomics ·Review· Introduction Alzheimer's disease (AD) is becoming more prevalent due to the increasing population of people aged over 65 [1] .It is estimated that it will affect 66 million by 2030 and 115 million by 2050 worldwide if no effective therapeutic strategies are found [2] . Clinically, AD is characterized by cognitive impairment, progressive disturbance of daily activities, many neuropsychiatric symptoms, and behavioral deterioration [3][4][5][6][7][8] . Pathologically, it is characterized by deposition of extracellular neuritic plaques composed of β-amyloid (Aβ) [9] and intracellular neurofibrillary tangles (NFTs) consisting of a hyperphosphorylated form of the microtubule-associated protein tau [10][11][12] . Besides, loss of neurons and synapses is also a pathological hallmark of AD [13][14][15] . The worldwide cost of dementia is huge and expected to skyrocket in the next few years. AD may become one of the most marked social, health, and economic challenges in the twenty-fi rst century [16] .Clinically, the procedure for the diagnosis of AD is diffi cult and complex. Neuropsychological tests, such as the mini-mental state examination, magnetic resonance imaging of hippocampal volume, and clinical assessment, are used to aid in diagnosis. However, a defi nitive diagnosis of AD requires confirmation at autopsy. It is estimated to take 8-10 years or longer before mild cognitive impairment (MCI) develops into AD [17,18] . Meanwhile, intervention therapies work most effectively in the early stage of AD. Thus, it is urgent and feasible to seek novel specifi c biomarkers to aid in diagnosis and the evaluation of treatments [19] . Surrounding the brain and spinal cord, cerebrospinal fluid (CSF) is an ideal source refl ecting biochemical changes in the brain of the AD patient [20] . Extensive studies have focused on seeking AD biomarkers in CSF.A comprehensive search of the Web of Science (Janua...

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Aβ40 Oligomers Identified as a Potential Biomarker for the Diagnosis of Alzheimer's Disease

Cited by 96 publications

References 37 publications

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

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

New Frontiers in Alzheimer's Disease Diagnosis

Cerebrospinal fluid biomarkers of Alzheimer’s disease

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