A novel peptidomics approach to detect markers of Alzheimer’s disease in cerebrospinal fluid

Wijte, Dorien; McDonnell, Liam A.; Balog, Crina I. A.; Bossers, Koen; Deelder, André M.; Swaab, Dick F.; Verhaagen, Joost; Mayboroda, Oleg A.

doi:10.1016/j.ymeth.2012.03.018

Cited by 49 publications

(41 citation statements)

References 33 publications

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“…These differences can be used to develop biomarkers of disease and provide insights into disease pathogenesis. Feasibility of a proteomics approach as well as disease-relevant changes have been described in both plasma (12)(13)(14) and cerebrospinal fluid (15)(16)(17), highlighting the utility of proteomics in biomarker development. We, and others, have also demonstrated the potential for this approach in identifying neurodegenerative-specific changes in postmortem brain tissues.…”

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confidence: 99%

U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer’s disease

Bai

Hales

Chen³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

275

380

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Deposition of insoluble protein aggregates is a hallmark of neurodegenerative diseases. The universal presence of β-amyloid and tau in Alzheimer's disease (AD) has facilitated advancement of the amyloid cascade and tau hypotheses that have dominated AD pathogenesis research and therapeutic development. However, the underlying etiology of the disease remains to be fully elucidated. Here we report a comprehensive study of the human brain-insoluble proteome in AD by mass spectrometry. We identify 4,216 proteins, among which 36 proteins accumulate in the disease, including U1-70K and other U1 small nuclear ribonucleoprotein (U1 snRNP) spliceosome components. Similar accumulations in mild cognitive impairment cases indicate that spliceosome changes occur in early stages of AD. Multiple U1 snRNP subunits form cytoplasmic tangle-like structures in AD but not in other examined neurodegenerative disorders, including Parkinson disease and frontotemporal lobar degeneration. Comparison of RNA from AD and control brains reveals dysregulated RNA processing with accumulation of unspliced RNA species in AD, including myc boxdependent-interacting protein 1, clusterin, and presenilin-1. U1-70K knockdown or antisense oligonucleotide inhibition of U1 snRNP increases the protein level of amyloid precursor protein.Thus, our results demonstrate unique U1 snRNP pathology and implicate abnormal RNA splicing in AD pathogenesis.proteomics | liquid chromatography-tandem mass spectrometry | U1A | RNA-seq | premature cleavage and polyadenylation

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mentioning

confidence: 99%

U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer’s disease

Bai

Hales

Chen³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

275

380

View full text Add to dashboard Cite

show abstract

“…Wijte et al, (2012) conducted a study on peptidome analysis of CSF from AD post-mortem brains and respective controls, and concluded with results of difference in profiles of endogenous peptides and protein bound peptide fractions [85]. The discriminating factors included VGF nerve growth factor inducible precursor, and complement C4 precursor, whereas the discriminating peptides in the proteinbound fraction were identified as VGF nerve growth factor inducible precursor, and alpha-2-HS-glycoprotein [86].…”

Section: Randomised Clinical Trialsmentioning

confidence: 99%

Exploring Biomarkers for Alzheimer’s Disease

Sharma¹

2016

JCDR

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“…This study used immunoproteomic approach and identified Aβ1-42 as a potential biomarker for AD. An additional study employed a combination of sample preparation methods, including enrichment of free endogenous peptides produced by proteolysis and peptides noncovalently bound to proteins, to perform a peptidome analysis of postmortem CSF of AD patients and control individuals (Wijte et al, 2012). VGF nerve growth factor inducible precursor and complement C4 precursor were identified in the enriched free peptide fraction, whereas in the protein-bound fraction VGF nerve growth factor inducible precursor and alpha-2-HS-glycoprotein were identified (Wijte et al, 2012).…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…An additional study employed a combination of sample preparation methods, including enrichment of free endogenous peptides produced by proteolysis and peptides noncovalently bound to proteins, to perform a peptidome analysis of postmortem CSF of AD patients and control individuals (Wijte et al, 2012). VGF nerve growth factor inducible precursor and complement C4 precursor were identified in the enriched free peptide fraction, whereas in the protein-bound fraction VGF nerve growth factor inducible precursor and alpha-2-HS-glycoprotein were identified (Wijte et al, 2012). In order to assess the potential of early AD diagnosis through peptidome analysis and to identify additional AD biomarkers, capillary electrophoresis-MS has been developed which reliably detects 1104 low molecular weight peptides in CSF ( Jahn et al, 2011).…”

Section: Alzheimer's Diseasementioning

confidence: 99%