High-resolution serum proteomic profiling of Alzheimer disease samples reveals disease-specific, carrier-protein-bound mass signatures
Lopez MF, Mikulskis A, Kuzdzal S, Bennett DA, Kelly J, Golenko E, DiCesare J, Denoyer E et al.. Clinical chemistry, 2005-08-04
Topic: Amyloid, tau and blood-test diagnosis
Background Researchers typically search for disease markers using a "targeted" approach in which a hypothesis about the disease mechanism is tested and experimental results either confirm or disprove the involvement of a particular gene or protein in the disease. Recently, there has been interest in developing disease diagnostics based on unbiased quantification of differences in global patterns of protein and peptide masses, typically in blood from individuals with and without disease. We combined a suite of methods and technologies, including novel sample preparation based on carrier-protein capture and biomarker enrichment, high-resolution mass spectrometry, a unique cohort of well-characterized persons with and without Alzheimer disease (AD), and powerful bioinformatic analysis, that add statistical and procedural robustness to biomarker discovery from blood. Methods Carrier-protein-bound peptides were isolated from serum samples by affinity chromatography, and peptide mass spectra were acquired by a matrix-assisted laser desorption/ionization (MALDI) orthogonal time-of-flight (O-TOF) mass spectrometer capable of collecting data over a broad mass range (100 to >300,000 Da) in a single acquisition. Discriminatory analysis of mass spectra was used to process and analyze the raw mass spectral data. Results Coupled with the biomarker enrichment protocol, the high-resolution MALDI O-TOF mass spectra provided informative, reproducible peptide signatures. The raw mass spectra were analyzed and used to build discriminant disease models that were challenged with blinded samples for classification. Conclusions Carrier-protein enrichment of disease biomarkers coupled with high-resolution mass spectrometry and discriminant pattern analysis is a powerful technology for diagnostics and population screening. The mass fingerprint model successfully classified blinded AD patient and control samples with high sensitivity and specificity.
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APA 7th
Lopez, M. F., Mikulskis, A., Kuzdzal, S., Bennett, D. A., Kelly, J., Golenko, E., et al. (2005). High-resolution serum proteomic profiling of Alzheimer disease samples reveals disease-specific, carrier-protein-bound mass signatures. Clinical chemistry. https://doi.org/10.1373/clinchem.2005.053090
Vancouver
Lopez MF, Mikulskis A, Kuzdzal S, Bennett DA, Kelly J, Golenko E, et al. High-resolution serum proteomic profiling of Alzheimer disease samples reveals disease-specific, carrier-protein-bound mass signatures. Clinical chemistry. 2005. doi:10.1373/clinchem.2005.053090. PMID: 16081505.
BibTeX
@article{lopez2005-16081505,
author = {Lopez, M. F. and Mikulskis, A. and Kuzdzal, S. and Bennett, D. A. and Kelly, J. and Golenko, E. and DiCesare, J. and Denoyer, E. and others},
title = {{High-resolution serum proteomic profiling of Alzheimer disease samples reveals disease-specific, carrier-protein-bound mass signatures}},
journal = {Clinical chemistry},
year = {2005},
doi = {10.1373/clinchem.2005.053090},
pmid = {16081505},
url = {https://doi.org/10.1373/clinchem.2005.053090}
}
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Key findings
- Background Researchers typically search for disease markers using a "targeted" approach in which a hypothesis about the disease mechanism is tested and experimental results either confirm or disprove the involvement of a particular gene or protein in the disease.
- Results Coupled with the biomarker enrichment protocol, the high-resolution MALDI O-TOF mass spectra provided informative, reproducible peptide signatures.
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Study details
- Evidence strengthModerate
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Clinical chemistry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2005 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16081505) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
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