Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders

Abdi, Fadi; Quinn, Joseph F.; Jankovic, Joseph; McIntosh, Martin W.; Leverenz, James B.; Peskind, Elaine R.; Nixon, Randal R.; Nutt, John G.; Chung, Katherine; Zabetian, Cyrus P.; Samii, Ali; Lin, Melanie; Hattan, Stephen J.; Pan, Catherine; Wang, Yan; Jin, Jinghua; Zhu, David C.; Li, G. Jane; Liu, Yan; Waichunas, Dana; Montine, Thomas J.; Zhang, Jing

doi:10.3233/jad-2006-9309

Cited by 360 publications

(341 citation statements)

References 46 publications

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“…Although the level of DBP in CSF has been known to be increased in AD patients, and several lines of evidence have suggested that DBP plays a role in AD, 11,15,16,32 there is no direct evidence of whether or how DBP affects AD-related pathology. Our data clearly show that DBP interacts directly with Ab and reduces the formation of aggregated Ab.…”

Section: Discussionmentioning

confidence: 98%

“…As many Ab-binding proteins, such as TTR, apoE, apoJ, and apoA1, are known to accumulate with Ab in amyloid No Ab bands were detected in the littermate mice; n ¼ 4 each cases deposits 5,17 and the level of DBP in CSF is increased in AD patients, 11,15,16 we examined whether DBP is present in the amyloid plaques of brains from AD patients and transgenic animal model of AD. We double-stained human AD and control brain with antibodies against Ab (4G8) and DBP.…”

Section: Resultsmentioning

confidence: 99%

“…32,38,39 Many studies have also shown alterations in the concentration of DBP in the CSF of AD patients, who demonstrated upregulation of DBP expression. 11,15,16 Based on these reports, Ab-binding proteins, including DBP, might provide effective diagnostic tools or biomarkers for AD. 32,38,39 It has been suggested that upregulation of neuroprotective and Ab-sequestering proteins, such as ADNP and cystatin C, in response to AD represents an intrinsic compensatory response that may counteract the progression of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…Several other studies also have shown that the level of DBP in CSF is increased in AD patients and suggested that this plays a role in the pathology of AD. 15,16 However, the functions of extracellular DBP in AD have not yet been elucidated.…”

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confidence: 99%

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Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology

et al. 2012

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The level of vitamin D-binding protein (DBP) is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD), suggesting a relationship with its pathogenesis. In this study, we investigated whether and how DBP is related to AD using several different approaches. A pull-down assay and a surface plasmon resonance binding assay indicated direct interactions between purified DBP and amyloid beta (Ab), which was confirmed in the brain of AD patients and transgenic AD model mice by immunoprecipitation assay and immunohistochemical double-staining method. Moreover, atomic force microscopic examination revealed that DBP reduced Ab aggregation in vitro. DBP also prevented Ab-mediated death in cultured mouse hippocampal HT22 cell line. Finally, DBP decreased Ab-induced synaptic loss in the hippocampus and rescued memory deficits in mice after injection of Ab into the lateral ventricle. These results provide converging evidence that DBP attenuates the harmful effects of Ab by a direct interaction, and suggest that DBP is a promising therapeutic agent for the treatment of AD.

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Section: Discussionmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology

et al. 2012

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“…10). It is also encouraging that many of the 81 proteins have already been reported as potential biomarkers for AD by multiple independent groups [2,20,28,31,36,[58][59][60][61]. Indeed, because none of these previously reported candidate biomarkers have been vetted sufficiently to be applied in clinical trials, they will have to be studied further: individually and in combination; in larger cohorts and in different diseases.…”

Section: Alternative and Evolving Strategies For Peptide Identificationmentioning

confidence: 99%

P1–206: Quantitative label‐free proteomics for discovery of biomarkers in cerebrospinal fluid: Assessment of technical and inter‐individual variation

Perrin

Payton

Malone

et al. 2013

Alzheimer's & Dementia

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Background: Biomarkers are required for pre-symptomatic diagnosis, treatment, and monitoring of neurodegenerative diseases such as Alzheimer's disease. Cerebrospinal fluid (CSF) is a favored source because its proteome reflects the composition of the brain. Ideal biomarkers have low technical and inter-individual variability (subject variance) among control subjects to minimize overlaps between clinical groups. This study evaluates a process of multi-affinity fractionation (MAF) and quantitative label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) for CSF biomarker discovery by (1) identifying reparable sources of technical variability, (2) assessing subject variance and residual technical variability for numerous CSF proteins, and (3) testing its ability to segregate samples on the basis of desired biomarker characteristics.

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Potential Applications and Limitations of Proteomics in the Study of Neurological Disease

Kinoshita¹,

Uo²,

Jayadev³

et al. 2006

Arch Neurol

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Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders

Cited by 360 publications

References 46 publications

Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology

Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology

P1–206: Quantitative label‐free proteomics for discovery of biomarkers in cerebrospinal fluid: Assessment of technical and inter‐individual variation

Potential Applications and Limitations of Proteomics in the Study of Neurological Disease

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