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Alzheimer's disease biomarker discovery using SOMAscan multiplexed protein technology
Open accessAbstract
Blood proteins and their complexes have become the focus of a great deal of interest in the context of their potential as biomarkers of Alzheimer's disease (AD). We used a SOMAscan assay for quantifying 1001 proteins in blood samples from 331 AD, 211 controls, and 149 mild cognitive impaired (MCI) subjects. The strongest associations of protein levels with AD outcomes were prostate‐specific antigen complexed to α1‐antichymotrypsin (AD diagnosis), pancreatic prohormone (AD diagnosis, left entorhinal cortex atrophy, and left hippocampus atrophy), clusterin (rate of cognitive decline), and fetuin B (left entorhinal atrophy). Multivariate analysis found that a subset of 13 proteins predicted AD with an accuracy of area under the curve of 0.70. Our replication of previous findings provides further evidence that levels of these proteins in plasma are truly associated with AD. The newly identified proteins could be potential biomarkers and are worthy of further investigation.
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“novel and highly sensitive high‐throughput protein arrays, such as aptamer‐based technologies, immunobased proximity extension assays, or antibody suspension beads arrays, which can readily measure large sets of protein libraries in CSF and blood samples. 132 , 133 , 134 , 135 , 136 , 137 , 138”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [132]
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“The coverage of proteins on the platform has taken into account proteins known to be relevant to human disease, including neurodegenerative diseases55 and cardiovascular diseases56; thus it has been widely used for biomarker discovery.”
From Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders (2021) · cites this paper as [55]
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Self-citationCerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages
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“According to the original results of the Sattlecker and colleagues [15] and the results of this study, factor XI (FXI) levels are increased in the plasma of the AddNeuroMed cohort patients diagnosed with probableAD,asmeasuredbytheSOMAscanassay.”
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“FB itself is essential for mammalian fertilization (10, 11) and a strong biomarker for Alzheimer’s disease (12).”
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“One of the highlighted proteins was FCN2 (Ficolin-2), previously associated with brain atrophy, which is reduced in insulin resistance and its level showed a negative correlation with CSF Aβ levels in the insulin-resistant group [54, 55].”
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“…level was determined through Myriad RBM-Luminex xMAP-190 (Hu et al., 2012), Myriad RBM-Luminex xMAP-146 analytes (Nazeri et al., 2014), Myriad RBM-Luminex xMAP-151 analytes (Doecke et al., 2012), and Slow Off-rate Modified Aptamer (SOMAmer) –“ SOMAscan ” -1001 analyte (Sattlecker et al., 2014).”
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“SOMAscan is an aptamer-based platform which transforms individual protein signals into corresponding chemically-modified nucleotide signals that can be quantified by relative fluorescence on DNA microarrays (Gold et al., 2010).”
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“Two studies utilizing plasma samples have been conducted on Alzheimer's patients, both of which have found clusterin and pancreatic prohormone to be a potential biomarker for AD [9,10].”
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Self-citationA correlativity study of plasma APL1β28 and clusterin levels with MMSE/MoCA/CASI in aMCI patients
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Current Methods in Clinical Alzheimer’s Disease Research and Diagnosis
Kodosaki, E., Zetterberg, H., & Heslegrave, A. (2025) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-025-00789-3 · Cited by 5
“A variety of studies have used that technology in different settings, with findings that correlate with studies using different methods and discovering novel targets [30–33].”
Dallaire‐Théroux, C., Denis, H. L., Cottez, R. J., Tremblay, C., Provencher, A., Valentin‐Escalera, J., Leclerc, M., Loiselle, A., Tournissac, M., Potvin, O., et al. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71097 · Cited by 6
A deep joint-learning proteomics model for diagnosis of six conditions associated with dementia
An, L., Binette, A. P., Hristovska, I., Vilkaite, G., Xiao, Y., Zendehdel, R., Dong, Z., Smets, B., Saloner, R., Tasaki, S., et al. (2026) · Nature Medicine · doi:10.1038/s41591-026-04303-y · Cited by 11
“Plasma proteomics represent a promising tool toward this aim, allowing robust surveillance of thousands of potential biomarkers and relevant functional effectors with a single blood draw 14 .”
Leng, Y., Ding, H., Ang, T. F. A., Au, R., Doraiswamy, P. M., & Liu, C. (2025) · The Journal of Prevention of Alzheimer s Disease · doi:10.1016/j.tjpad.2024.100021 · Cited by 5
Nanostructure-Based Molecules as Diagnostic and Theranostic Tools in Alzheimer’s Disease
Suthar, T., & Jain, K. (2023) · Springer eBooks · doi:10.1007/978-981-99-6038-5_6 · Cited by 5
Fernandez, N., Perumal, D., Rahman, A. H., Kim‐Schulze, S., Yesil, J., Auclair, D., Adams, H., Parekh, S. S., Gnjatic, S., & Cho, H. J. (2022) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2022.07.001 · Cited by 5
Kuchenbecker, L. A., Thompson, K. J., Hurst, C. D., Huang, Y.-N., Heckman, M. G., Reddy, J. S., Nguyen, T., Casellas, H. L., Sotelo, K. D., Reddy, D. J., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70505 · Cited by 5
Shapiro, A. L. B., Coughlan, C. M., Bettcher, B. M., PAULEY, M. E., Kim, J., Bjornstad, P., RAJIC, B. S., Truong, J., Bell, C., Choi, Y. J., et al. (2024) · Endocrines · doi:10.3390/endocrines5020014 · Cited by 5
“Stored ( − 80 ◦ C; polypropylene tubes) fasting plasma samples were assessed for biomarkers of AD via the Quanterix Simoa platform [39], including the Neurology 4-Plex A Advantage Kit measuring A β 40, A β 42, GFAP, and NfL, and the pTau181 Advantage V2 Assay Kit for the additional measurement of…”
MethodCruchaga, C., Sung, Y. J., Yang, C., Wang, F., Suhy, A., Norton, J. B., Novotny, B. C., Eteleeb, A. M., Fagan, A. M., Bateman, R. J., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-923492/v1 · Cited by 4
Snyder, P. J. (2015) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2015.01.001 · Cited by 3
An, L., Binette, A. P., Hristovska, I., Vilkaite, G., Xiao, Y., Zendehdel, R., Dong, Z., Smets, B., Saloner, R., Tasaki, S., et al. (2025) · medRxiv · doi:10.1101/2025.06.27.25330344 · Cited by 3
“Plasma proteomics represent a promising tool toward this aim, allowing robust surveillance of thousands of potential biomarkers and relevant functional effectors with a single blood draw 27–29 .”
Systematic comparison of colocalization methods using protein quantitative trait lociPreprint
Hwang, S., Pullin, J. M., Wallace, C., Whittaker, J. C., & Burgess, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.07.686776 · Cited by 3
Serum proteomics reveals APOE dependent and independent protein signatures in Alzheimer’s disease
Frick, E. A., Emilsson, V., Jonmundsson, T., Steindorsdottir, A. E., Johnson, E. C. B., Puerta, R., Dammer, E. B., Shantaraman, A., Cano, A., Boada, M., et al. (2023) · doi:10.1101/2023.11.08.23298251 · Cited by 3
Zhou, Z., Li, Y., Zhu, L., Li, H. Y., Wang, N., Zhou, H., Zhang, J., Fang, L., & Li, S. (2026) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5c00754 · Cited by 2
Unleashing the Power of Multiomics: Unraveling the Molecular Landscape of Peripheral Neuropathy
Choi, J. Y., Tang, Z., Dong, W., Ulibarri, J., Mehinovic, E., Thomas, S., Höke, A., & Jin, S. C. (2025) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.70019 · Cited by 2
“…platform uses fluorescently labeled DNA aptamers—short single-stranded nucleic acids that fold into unique three-dimensional structures—to selectively bind up to 11,000 molecular targets, facilitating the discovery of novel biomarker candidates in multiple neurodegenerative disorders [87–90].”
Chiam, J. T. W., Lunnon, K., Voyle, N., Proitsi, P., Coppola, G., Geschwind, D. H., Nelson, S., Johnston, C., Soininen, H., Kłoszewska, I., et al. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150289 · Cited by 2
Self-citationModifications ondulantes du protéome du plasma humain au long de la vie
Guerrera, I. C. (2020) · médecine/sciences · doi:10.1051/medsci/2020150 · Cited by 2
Omic-Based Biomarkers Discovery in Alzheimer’s Disease: High-Throughput Approaches
Kalli, Ε. G. (2023) · Springer eBooks · doi:10.1007/978-3-319-75479-6_8-1 · Cited by 2
Xu, J., Bankov, G., Kim, M. G., Wretlind, A., Lord, J., Green, R., Hodges, A., Hye, A., Aarsland, D., Velayudhan, L., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.18.995464 · Cited by 2
Self-citationBlood-based protein biomarkers in definite frontotemporal dementia: a case-control studyPreprint
Teunissen, C. E., del Campo, M., Peeters, C. F. W., Meeter, L. H. H., Seelaar, H., Simmelink, M. J. A., Ramakers, I. H. G. B., Middelkoop, H. A. M., Deyn, P. P. D., Claessen, J., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1534214/v1 · Cited by 2
Blood biomarkers of Alzheimer’s disease: findings from proteomics
Wang, Y., Niu, X., Zhen, W., Zhang, B., Chen, L., Liu, Y., Sun, W., & Peng, D. (2025) · Postgraduate Medical Journal · doi:10.1093/postmj/qgaf039 · Cited by 1
Identifying Links between Alzheimer’s Disease and Type 2 Diabetes through Proteomics
Chen, T. N., Orr, A. L., Orr, A. G., & Vacanti, N. M. (2025) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5c00404 · Cited by 1
Hepatic dysfunction and long-term risk of neurodegenerative diseases: A UK Biobank-based analysis
Su, W., Duan, Q., He, S.-Y., Liu, R., Wen, X., Zhang, N., Gu, X., Yin, K., Chen, T., Cao, B., et al. (2026) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2026.106252 · Cited by 1
Pillai, J. A., Zhu, A., Ma, C., Wang, M., Yang, Y., Bekris, L. M., Khrestian, M., DiFilippo, F. P., Nasrallah, M., Burberry, A., et al. (2026) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.70532 · Cited by 1
“This approach uses chemically modified nucleotides to transform a protein signal into a nucleotide signal that can be quantified using relative fluorescence on microarrays [24].”
Searching for Neurodegeneration in the Blood of Patients With Alzheimer Disease
Galasko, D. R. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.0010 · Cited by 1
AptaBlocks Online: A Web-Based Toolkit for the In Silico Design of Oligonucleotide Sticky Bridges
Hoinka, J., Wang, Y., & Przytycka, T. M. (2020) · Journal of Computational Biology · doi:10.1089/cmb.2019.0470 · Cited by 1
“Oligonucleotides are rapidly emerging as competitive and highly efficient alternatives to tradi-tional therapeutics and are increasingly employed in a growing array of biotechnological applications (Keefe et al., 2010; Thiel and Giangrande, 2010; Sun et al., 2014; Zhou and Rossi, 2017).”
BackgroundThe urgent and global need for democratized blood-based biomarker diagnostics in Alzheimer's disease
Quinn, S. D. (2025) · The Journal of Precision Medicine Health and Disease · doi:10.1016/j.premed.2025.100002 · Cited by 1
Advances in Diagnosis and Prognosis of Parkinson Disease
Parnetti, L., & Bellomo, G. (2023) · Neurology · doi:10.1212/wnl.0000000000207724 · Cited by 1
Kuchenbecker, L. A., Thompson, K. J., Hurst, C. D., Opdenbosch, B. M., Heckman, M. G., Reddy, J. S., Nguyen, T., Casellas, H. L., Sotelo, K. D., Reddy, D. J., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.27.605373 · Cited by 1
“…assay includes 949 proteins that can also be detected with the 7k assay, we obtained a publicly available SomaScan 1.1k plasma proteome dataset from ANMerge 39,40 European study participants with diagnoses of AD dementia or CU that were utilized as a replication dataset ( Supplementary Table 1 ).”
MethodAdeola, H. A., & Robinson, R. A. S. (2025) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.5c00074 · Cited by 1
Tarnanas, I., Tsolaki, A., Wiederhold, M. D., Wiederhold, B. K., & Tsolaki, M. (2015)
Self-citationBegić, E., Hadžidedić, S., Kulaglić, A., Ramić-Brkić, B., Begić, Z., & Čaušević, M. (2018) · Cardiologia Croatica · doi:10.15836/ccar2018.435
AptaBlocks Online - A web-based toolkit for the in-silico assembly of RNA complexesPreprint
Hoinka, J., Wang, Y., & Przytycka, T. M. (2019) · arXiv (Cornell University) · doi:10.48550/arxiv.1903.05657
“These include, but not limited to next-generation biosensors [5, 6, 7] and, more recently, in in vitro and in vivo delivery systems for individualized medicine approaches which frequently face the challenge of delivering a drug across a biological membrane to reach their target.”
BackgroundSOMAscan proteomics of Zika-infected cells
Coombs, K. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820268-5.00029-8
Larner, A. J. (2015) · Springer eBooks · doi:10.1007/978-3-319-16697-1_4
Kuroda, S., & Fujita, S. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.737033740.793570208
Yemima, P., & Johansyah, C. L. (2021) · JIMKI Jurnal Ilmiah Mahasiswa Kedokteran Indonesia · doi:10.53366/jimki.v9i2.477
Metadata
- Authors
- Sattlecker, M., Kiddle, S. J., Newhouse, S., Proitsi, P., Nelson, S., Williams, S., Johnston, C., Killick, R., Simmons, A., Westman, E., Hodges, A., Soininen, H., Kłoszewska, I., Mecocci, P., Tsolaki, M., Vellas, B., Lovestone, S., AddNeuroMed Consortium, & Dobson, R. J. B.
- Affiliations
- King's College London (GB)
- SomaLogic (United States) (US)
- University of Eastern Finland (FI)
- Medical University of Lodz (PL)
- University of Perugia (IT)
- Aristotle University of Thessaloniki (GR)
- Inserm (FR)
- Corresponding author
- Dobson, Richard J.B.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2014-04-28
- Volume
- 10
- Issue
- 6
- Pages
- 724-734
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2035892094
- Cited by
- 223
- References
- 54
- Citations by year
- 2026: 7 · 2025: 19 · 2024: 19 · 2023: 15 · 2022: 13 · 2021: 26 · 2020: 22 · 2019: 16 · 2018: 18 · 2017: 13 · 2016: 20 · 2015: 26 · 2014: 9
- FWCI
- 17.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Portal (King's College London) (acceptedVersion, cc-by-nc-nd)
- UCL Discovery (University College London) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, cc-by-nc-nd)
- Funders
- NIHR Newcastle Biomedical Research Centre
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, biomarkers
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Blood Proteins, Brain, Female, Humans, Magnetic Resonance Imaging, Male, ROC Curve, Cohort Studies, Biomarkers, Logistic Models, Proteomics, Cognitive Dysfunction
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