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Analysis of institutional authors

Del Campo, MartaCorresponding AuthorHerradon, GonzaloAuthor

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February 22, 2025
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Article

CSF proteome profiling across the Alzheimer's disease spectrum reflects the multifactorial nature of the disease and identifies specific biomarker panels

Publicated to: Nat Aging. 2 (11): 1040-+ - 2022-11-01 2(11), DOI: 10.1038/s43587-022-00300-1

Authors:

del Campo, M; Peeters, CFW; Johnson, ECB; Vermunt, L; Hok-A-Hin, YS; van Nee, M; Chen-Plotkin, A; Irwin, DJ; Hu, WT; Lah, JJ; Seyfried, NT; Dammer, EB; Herradon, G; Meeter, LH; van Swieten, J; Alcolea, D; Lleo, A; Levey, AI; Lemstra, AW; Pijnenburg, YAL; Visser, PJ; Tijms, BM; van der Flier, WM; Teunissen, CE
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Affiliations

Barcelonasseta Brain Res Ctr BBRC, Pasqual Maragall Fdn, Barcelona, Spain - Author
Emory Univ, Goizueta Alzheimers Dis Res Ctr, Atlanta, GA USA - Author
Emory Univ, Sch Med, Dept Neurol, Atlanta, GA USA - Author
Erasmus MC, Alzheimer Ctr, Rotterdam, Netherlands - Author
Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, New Brunswick, NJ USA - Author
Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Med Ctr,Amsterdam Neurosci,Locat VUmc, Amsterdam, Netherlands - Author
Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Dept Epidemiol & Data Sci, Med Ctr,Locat VUmc, Amsterdam, Netherlands - Author
Univ Amsterdam, Dept Clin Chem, Neurochem Lab, Med Ctr,Locat VUmc,Amsterdam Neurosci, Amsterdam, Netherlands - Author
Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA USA - Author
Univ San Pablo CEU, CEU Univ, Fac Farm, Dept Ciencias Farmaceut & Salud, Boadilla Del Monte, Spain - Author
Wageningen Univ & Res, Math & Stat Methods Grp Biometris, Wageningen, Netherlands - Author
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Abstract

Development of disease-modifying therapies against Alzheimer's disease (AD) requires biomarkers reflecting the diverse pathological pathways specific for AD. We measured 665 proteins in 797 cerebrospinal fluid (CSF) samples from patients with mild cognitive impairment with abnormal amyloid (MCI(A beta+): n = 50), AD-dementia (n = 230), non-AD dementias (n = 322) and cognitively unimpaired controls (n = 195) using proximity ligation-based immunoassays. Here we identified >100 CSF proteins dysregulated in MCI(A beta+) or AD compared to controls or non-AD dementias. Proteins dysregulated in MCI(A beta+) were primarily related to protein catabolism, energy metabolism and oxidative stress, whereas those specifically dysregulated in AD dementia were related to cell remodeling, vascular function and immune system. Classification modeling unveiled biomarker panels discriminating clinical groups with high accuracies (area under the curve (AUC): 0.85-0.99), which were translated into custom multiplex assays and validated in external and independent cohorts (AUC: 0.8-0.99). Overall, this study provides novel pathophysiological leads delineating the multifactorial nature of AD and potential biomarker tools for diagnostic settings or clinical trials. This study identifies CSF proteins specifically dysregulated along the AD continuum that reflect the multifactorial nature of disease progression. Some of these CSF proteins were used to build biomarker panels with high diagnostic accuracies.
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Keywords

A-betaAlzheimer diseaseAmyloid beta-peptidesBiomarkersCognitive dysfunctionDementiaDiagnosisDiscoverHumansLewy bodiesManagementNational instituteProteomeRecommendationsResearch criteriaTau

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Nat Aging due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Geriatrics and Gerontology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 6.05. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 4.52 (source consulted: FECYT Mar 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-05, the following number of citations:

  • WoS: 54
  • Scopus: 57
  • Europe PMC: 44
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-05:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 93.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 98 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 47.
  • The number of mentions on the social network X (formerly Twitter): 62 (Altmetric).
  • The number of mentions in news outlets: 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Netherlands; Sweden; United States of America.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (del Campo Milán, Marta) .

the author responsible for correspondence tasks has been del Campo Milán, Marta.

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Awards linked to the item

This research is part of the neurodegeneration research program of Amsterdam Neuroscience. This study was supported by Alzheimer Nederland (WE.03-2018-05, M.d.C. and C.E.T.) and Selfridges Group Foundation (NR170065, M.d.C. and C.E.T.). M.d.C. and G.H. are supported by the attraction talent fellowship of Comunidad de Madrid (2018-T2/BMD-11885) and San Pablo CEU University. D.A. acknowledges support from Institute of Health Carlos III (PI18/00435, INT19/00016) and the Department of Health Generalitat de Catalunya PERIS program (SLT006/17/125). Collection of patients samples and data from Penn University (A.C.-P. and D.J.I.) was supported by different funding sources, including National Institute on Aging NINDS R01-NS109260-01A1, P01-AG066597, P30-AG072979 (formerly P30-AG10124) and U19-AG062418-03 (formerly NINDSP50-NS053488-09). Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The chair (W.M.v.d.F.) is supported by the Pasman stichting. The clinical database structure was developed with funding from Stichting Dioraphte. Research programs of W.M.v.d.F. have been funded by ZonMW, NWO, EU-FP7, EU-JPND, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health~Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbisfonds, stichting Equilibrio, Edwin Bouw fonds, Pasman stichting, stichting Alzheimer & Neuropsychiatrie Foundation, Philips, Biogen MA, Novartis-NL, Life-MI, AVID, Roche BV, Fujifilm and Combinostics. W.M.v.d.F. holds the Pasman chair. W.M.v.d.F. is a recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). All funding is paid to her institution. Research of C.E.T. is supported by the European Commission (Marie Curie International Training Network, grant agreement No. 860197 (MIRIADE)), Innovative Medicines Initiatives 3TR (Horizon 2020, grant 831434), EPND (IMI 2 Joint Undertaking (JU) under grant agreement 101034344) and JPND (bPRIDE), National MS Society (Progressive MS alliance) and Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands and Alzheimer Association. C.E.T. is a recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (3305095007) and Health~Holland, Topsector Life Sciences & Health (PPP allowance; LSHM20106). ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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