Prognostic polypeptide blood plasma biomarkers of Alzheimer's disease progression
Open accessAbstract
BACKGROUND: Patients with mild cognitive impairment (MCI) have varying risks of progression to Alzheimer's disease (AD). OBJECTIVE: To test the utility of the relative abundances of blood plasma polypeptides for predicting the risk of AD progression. METHODS: 119 blood plasma samples of patients with MCI with different outcomes (stable MCI and progressive MCI) were analyzed by untargeted, label-free shotgun proteomics. Predictive biomarkers of progressive MCI were selected by multivariate analysis, followed by cross-validation of the predictive model. RESULTS: The best model demonstrated the accuracy of ca. 79% in predicting progressive MCI. Sex differences of the predictive biomarkers were also assessed. We have identified some sex-specific protein biomarkers, e.g., alpha-2-macrogloblin (A2M), which strongly correlates with female AD progression but not with males. CONCLUSION: Significant sex bias in AD-specific biomarkers underscores the necessity of selecting sex-balanced cohort in AD biomarker studies, or using sex-specific models. Blood protein biomarkers are found to be promising for predicting AD progression in clinical settings.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Fibrinogen elevation in plasma and cerebrospinal fluid is an early biomarker of dementia risk and is associated with progression of cognitive decline in AD.
“Biomarker studies further support the notion that fibrinogen elevation in plasma and cerebrospinal fluid is an early biomarker of dementia risk and is associated with progression of cognitive decline in AD.39,45-48”
From Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models (2024) · cites this paper as [48]
The “Top proteome” blood analysis section reports elevated plasma fibrinogen-chain proteins in patients with progressive, rather than stable, mild cognitive impairment, supporting a link to AD progression. The Participants and prognostic-model sections describe prediction of AD onset after follow-up. The paper does not report elevated fibrinogen in cerebrospinal fluid or establish fibrinogen as a biomarker of dementia risk or measured cognitive decline; its introduction identifies different CSF biomarkers. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Multimodal techniques for diagnosis and prognosis of Alzheimer's disease
Perrin, R. J., Fagan, A. M., & Holtzman, D. M. (2009) · Nature · doi:10.1038/nature08538 · Cited by 702 · see citing works
Identifying and validating biomarkers for Alzheimer's disease
Humpel, C. (2011) · Trends in Biotechnology · doi:10.1016/j.tibtech.2010.09.007 · Cited by 484 · see citing works
On the Development of Plasma Protein Biomarkers
Surinova, S., Schiess, R., Hüttenhain, R., Cerciello, F., Wollscheid, B., & Aebersold, R. (2011) · Journal of Proteome Research · doi:10.1021/pr1008515 · Cited by 334 · cited 2× · see citing works
“This makes it a very challenging system to analyze with LC-MS that has a dynamic range of three to four orders of magnitude in direct (“discovery”) analysis and up to six orders in targeted analysis [12].”
BackgroundBlood-Based Biomarkers of Alzheimer's Disease: Challenging but Feasible
Thambisetty, M., & Lovestone, S. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.09.84 · Cited by 182 · see citing works
CSF biomarkers for mild cognitive impairment
Blennow, K. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01368.x · Cited by 151 · see citing works
Neuropathology of preclinical and clinical lateonset Alzheimer's disease
Troncoso, J. C., Cataldo, A. M., Nixon, R. A., Barnett, J. L., Lee, M. K., Checler, F., Fowler, D. R., Smialek, J. E., Crain, B., Martin, L. J., et al. (1998) · Annals of Neurology · doi:10.1002/ana.410430519 · Cited by 93 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Akuffo EL, Davis JB, Fox SM, Gloger IS, Hosford D, Kinsey EE, Jones NA, Nock CM, Roses AD, Saunders AM, Ske- hel JM, Smith MA, Cutler P (2008) The discovery and early validation of novel plasma biomarkers in mild-to-moderate Alzheimer's disease patients responding to treatment with rosiglitazone. Biomarkers 13, 618-636.
Cited by
Sorted by citations
Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics
Petersen, M. A., Ryu, J. K., & Akassoglou, K. (2018) · Nature reviews. Neuroscience · doi:10.1038/nrn.2018.13 · Cited by 527 · see citing works
Miller, S. R., Luxem, K., Lauderdale, K., Nambiar, P., Honma, P. S., Ly, K. K., Bangera, S., Bullock, M., Shin, J., Kaliss, N., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114870 · Cited by 24 · see citing works
“39,45-48 Notably, we found that genetic blockade of fibrinogen-microglia interactions in 5xFAD-Fgg γ 390–396A mice reduced virtually all the motif usage abnormalities found in 5xFAD mice.”
- Authors
- Yang, H., Lyutvinskiy, Y., Herukka, S.-K., Soininen, H., Rutishauser, D., & Zubarev, R. A.
- Affiliations
- Karolinska Institutet (SE)
- University of Eastern Finland (FI)
- Science for Life Laboratory (SE)
- ORCID
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2014-04-23
- Volume
- 40
- Issue
- 3
- Pages
- 659-666
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1588945080
- Cited by
- 52
- References
- 6
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 8 · 2020: 4 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 3 · 2015: 7 · 2014: 3 · 2013: 1
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Funders
- VINNOVA
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Alzheimerfonden
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- Alzheimer's disease progression, mild cognitive impairment
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Blood Proteins, Female, Humans, Male, Peptides, Proteins, Sex Factors, Mass Spectrometry, Cohort Studies, Biomarkers, Disease Progression, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
