Plasma and CSF biomarkers in a memory clinic: Head‐to‐head comparison of phosphorylated tau immunoassays
Open accessAbstract
Introduction: Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences. Methods: In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non‐AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aβ42/p‐tau) ratio. We performed a head‐to‐head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aβ42/p‐tau ratio. Results: All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non‐AD CSF profile group and significantly discriminated abnormal CSF Aβ42/p‐tau ratio. For plasma p‐tau biomarkers, the higher discrimination accuracy was shown by Janssen p‐tau217 ( r = 0.76; area under the curve [AUC] = 0.96), ADx p‐tau181 ( r = 0.73; AUC = 0.94), and Lilly p‐tau217 ( r = 0.73; AUC = 0.94). Discussion: Several plasma p‐tau biomarkers can be used in a specialized memory clinic as a stand‐alone biomarker to detect biologically‐defined AD. Highlights: Patients with an Alzheimer's disease cerebrospinal fluid (AD CSF) profile have higher plasma phosphorylated tau (p‐tau) levels than the non‐AD CSF profile group. All plasma p‐tau biomarkers significantly discriminate patients with an AD CSF profile from the non‐AD CSF profile group. Janssen p‐tau217, ADx p‐tau181, and Lilly p‐tau217 in plasma show the highest accuracy to detect biologically defined AD. Janssen p‐tau217, ADx p‐tau181, Lilly p‐tau217, Lilly p‐tau181, and UGot p‐tau231 in plasma show performances that are comparable to their CSF counterparts.
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?
Several recent studies have reported that plasma biomarkers have excellent diagnostic accuracy for AD, with sensitivity or specificity often exceeding 90%.
“Several recent studies have reported that plasma biomarkers have excellent diagnostic accuracy for AD, with sensitivity or specificity often exceeding 90% (refs. 4–10).”
From Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability (2024) · cites this paper as [9]
The Results section reports excellent discrimination of biologically defined AD by several plasma p-tau assays, with AUCs of 0.91–0.96. But AUC is not sensitivity or specificity: the Results refer those measures to Table S4 without giving their values in the available passages, so the claim that either often exceeds 90% is not established by our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHead-to-head studies indicate that different assays for p-tau181 vary substantially in their diagnostic performance and may not all perform inferiorly to GFAP in all contexts.
“However, it is important to emphasize that head-to-head studies indicate that different assays for p-tau181 vary substantially in their diagnostic performance9,10 and may not all perform inferiorly to GFAP in all contexts34,43.”
From Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability (2024) · cites this paper as [9]
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
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589 · see citing works
High performance plasma amyloid-β biomarkers for Alzheimer's disease
Nakamura, A., Kaneko, N., Villemagne, V. L., Kato, T., Doecke, J., Doré, V., Fowler, C., Li, Q.-X., Martins, R., Rowe, C., et al. (2018) · Nature · doi:10.1038/nature25456 · Cited by 1,681 · see citing works
Plasma β-amyloid in Alzheimer's disease and vascular disease
Janelidze, S., Stomrud, E., Palmqvist, S., Zetterberg, H., van Westen, D., Jeromin, A., Song, L., Hanlon, D., Tan Hehir, C. A., Baker, D., et al. (2016) · Scientific Reports · doi:10.1038/srep26801 · Cited by 626 · see citing works
Self-citationThijssen, E. H., La Joie, R., Strom, A., Fonseca, C., Iaccarino, L., Wolf, A., Spina, S., Allen, I. E., Cobigo, Y., Heuer, H., et al. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00214-3 · Cited by 607 · see citing works
Self-citationHansson, O., Edelmayer, R. M., Boxer, A. L., Carrillo, M. C., Mielke, M. M., Rabinovici, G. D., Salloway, S., Sperling, R., Zetterberg, H., & Teunissen, C. E. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12756 · Cited by 607 · see citing works
Self-citationMilà-Alomà, M., Ashton, N. J., Shekari, M., Salvadó, G., Ortiz-Romero, P., Montoliu-Gaya, L., Benedet, A. L., Karikari, T. K., Lantero-Rodriguez, J., Vanmechelen, E., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01925-w · Cited by 353 · cited 1× · see citing works
“9,10,12,14,17,18 The emergence of blood p-tau assays has occurred in parallel with the discovery of new CSF p-tau assays that quantify N-terminal tau species, thereby improving the diagnostic performance of the more widely used CSF assays targeting the mid-region tau and phosphorylation at T181.”
BackgroundSelf-citation
Flagged first, then by citations
Research works printed but not linked: 23
- [1]Blennow K Phenotyping Alzheimer’s disease with blood tests. Science. 2021; 373(6555): 626– 628. doi: 10.1126/SCIENCE.ABI5208 34353941 · DOI · Paper page
- [2]Shaw LM, Arias J, Blennow K, Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer’s disease. Alzheimers Dement. 2018; 14(11): 1505– 1521. doi: 10.1016/j.jalz.2018.07.220 30316776 PMC10013957 · DOI · Paper page
- [4]Verberk IMW, Slot RE, Verfaillie SCJ, Plasma amyloid as pre-screener for the earliest Alzheimer pathological changes. Ann Neurol. 2018; 84(5): 648– 658. doi: 10.1002/ana.25334 30196548 PMC6282982 · DOI · Paper page
- [5]Simrén J, Leuzy A, Karikari TK, The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer’s disease. Alzheimers Dement. 2021; 17(7): 1145– 1156. doi: 10.1002/alz.12283 33491853 PMC8359457 · DOI
- [7]Schindler SE, Bollinger JG, Ovod V, High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019; 93(17): e1647– e1659. doi: 10.1212/WNL.0000000000008081 31371569 PMC6946467 · DOI · Paper page
- [8]Keshavan A, Pannee J, Karikari TK, Population-based blood screening for preclinical Alzheimer’s disease in a British birth cohort at age 70. Brain. 2021; 144(2): 434– 449. doi: 10.1093/brain/awaa403 33479777 PMC7940173 · DOI
- [9]Janelidze S, Mattsson N, Palmqvist S, Plasma P-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia. Nat Med. 2020; 26(3): 379– 386. doi: 10.1038/s41591-020-0755-1 32123385 · DOI · Paper page
- [10]Karikari TK, Pascoal TA, Ashton NJ, Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020; 19(5): 422– 433. doi: 10.1016/S1474-4422(20)30071–5 32333900 · DOI · Paper page
- [11]Barthélemy NR, Horie K, Sato C, Bateman RJ. Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease. J Exp Med. 2020; 217(11): e1647– e1659. doi: 10.1084/jem.20200861 PMC7596823 32725127 · DOI · Paper page
- [12]Palmqvist S, Janelidze S, Quiroz YT, Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA. 2020; 324(8): 772. doi: 10.1001/jama.2020.12134 32722745 PMC7388060 · DOI · Paper page
- [13]Suárez-Calvet M, Karikari TK, Ashton NJ, Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer’s continuum when only subtle changes in Aβ pathology are detected. EMBO Mol Med. 2020; 12(12). 10.15252/emmm.202012921 PMC7721364 33169916 · DOI · Paper page
- [15]Benedet AL, Milà-Alomà M, Vrillon A, Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the Alzheimer disease continuum. JAMA Neurol. 2021; 78(12): 1471. doi: 10.1001/jamaneurol.2021.3671 34661615 PMC8524356 · DOI · Paper page
- [16]Ashton NJ, Janelidze S, Al Khleifat A, A multicentre validation study of the diagnostic value of plasma neurofilament light. Nat Commun. 2021; 12(1): 3400. doi: 10.1038/s41467-021-23620-z 34099648 PMC8185001 · DOI · Paper page
- [17]Thijssen EH, La Joie R, Wolf A, Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration. Nat Med. 2020; 26(3): 387– 397. doi: 10.1038/s41591-020-0762-2 32123386 PMC7101073 · DOI · Paper page
- [19]Triana-Baltzer G, Moughadam S, Slemmon R, Development and validation of a high-sensitivity assay for measuring p217+tau in plasma. 2021; 13(1) e12204. doi: 10.1002/dad2.12204 PMC8158165 34095436 · DOI
- [20]Ashton NJ, Pascoal TA, Karikari TK, Plasma p-tau231: a new biomarker for incipient Alzheimer’s disease pathology. Acta Neuropathol. 2021: 0123456789. doi: 10.1007/s00401-021-02275-6 PMC8043944 33585983 · DOI · Paper page
- [21]Puig-Pijoan A, García-Escobar G, Fernández-Lebrero A, The CORCOBIA study: cut-off points of Alzheimer’s disease CSF biomarkers in a clinical cohort. Neurol (English Ed). Published online August 9, 2022: 101890. doi: 10.1016/j.nrleng.2022.05.002 35961506 · DOI
- [22]Reisberg B, Ferris SH, De Leon MJ, Crook T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry. 1982; 139(9): 1136– 1139. doi: 10.1176/AJP.139.9.1136 7114305 · DOI
- [23]Rosenthal R, Rosnow RLR. Essentials of Behavioral Research: Methods and Data Analysis. 2nd ed. McGraw Hill; 1991.
- [24]Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B. 1995; 57(1): 289– 300. doi: 10.1111/j.2517-6161.1995.tb02031.x · DOI · Paper page
- [25]Teunissen CE, Verberk IMW, Thijssen EH, Blood-based biomarkers for Alzheimer’s disease: towards clinical implementation. Lancet Neurol. 2022; 21(1): 66– 77. doi: 10.1016/S1474-4422(21)00361-6 34838239 · DOI · Paper page
- [26]Zetterberg H, Blennow K. Blood biomarkers: democratizing Alzheimer’s diagnostics. Neuron. 2020; 106(6): 881– 883. doi: 10.1016/j.neuron.2020.06.004 32553204 · DOI
- [27]Bayoumy S, Verberk IMW, den Dulk B, Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231. Alzheimers Res Ther. 2021; 13(1): 198. doi: 10.1186/s13195-021-00939-9 34863295 PMC8645090 · DOI
Cited by
Sorted by citations
Blood biomarkers for Alzheimer’s disease in clinical practice and trials
Hansson, O., Blennow, K., Zetterberg, H., & Dage, J. (2023) · Nature Aging · doi:10.1038/s43587-023-00403-3 · Cited by 522 · see citing works
Self-citationHampel, H., Hu, Y., Cummings, J., Mattke, S., Iwatsubo, T., Nakamura, A., Vellas, B., O’Bryant, S., Shaw, L. M., Cho, M., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.05.017 · Cited by 283 · see citing works
Self-citationBrum, W. S., Cullen, N. C., Janelidze, S., Ashton, N. J., Zimmer, E. R., Therriault, J., Benedet, A. L., Rahmouni, N., Tissot, C., Stevenson, J., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00471-5 · Cited by 248 · see citing works
Self-citationSpecific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads
Salvadó, G., Ossenkoppele, R., Ashton, N. J., Beach, T. G., Serrano, G. E., Reiman, E. M., Zetterberg, H., Mattsson‐Carlgren, N., Janelidze, S., Blennow, K., et al. (2023) · EMBO Molecular Medicine · doi:10.15252/emmm.202217123 · Cited by 205 · see citing works
Self-citationAlzheimer’s Disease: Exploring the Landscape of Cognitive Decline
Tenchov, R., Sasso, J. M., & Zhou, Q. A. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00339 · Cited by 170 · see citing works
Montoliu-Gaya, L., Benedet, A. L., Tissot, C., Vrillon, A., Ashton, N. J., Brum, W. S., Lantero-Rodriguez, J., Stevenson, J., Nilsson, J., Sauer, M., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00405-1 · Cited by 122 · see citing works
Self-citationDiagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability
Therriault, J., Janelidze, S., Benedet, A. L., Ashton, N. J., Arranz Martínez, J., Gonzalez-Escalante, A., Bellaver, B., Alcolea, D., Vrillon, A., Karim, H., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00731-y · Cited by 112 · see citing works
Self-citationThe potential clinical value of plasma biomarkers in Alzheimer's disease
Blennow, K., Galasko, D., Perneczky, R., Quevenco, F., van der Flier, W. M., Akinwonmi, A., Carboni, M., Jethwa, A., Suridjan, I., & Zetterberg, H. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13455 · Cited by 75 · see citing works
Self-citationAbrol, A., Calhoun, V. D., & Initiative, T. A. D. N. (2025) · Human Brain Mapping · doi:10.1002/hbm.70391 · Cited by 3 · see citing works
- Authors
- Ashton, N. J., Puig‐Pijoan, A., Milà‐Alomà, M., Fernández‐Lebrero, A., García‐Escobar, G., González‐Ortiz, F., Kac, P. R., Brum, W. S., Benedet, A. L., Lantero‐Rodriguez, J., Day, T. A., Vanbrabant, J., Stoops, E., Vanmechelen, E., Triana‐Baltzer, G., Moughadam, S., Kolb, H., Ortiz‐Romero, P., Karikari, T. K., Minguillon, C., Hernández Sánchez, J. J., Navalpotro‐Gómez, I., Grau‐Rivera, O., María Manero, R., Puente‐Periz, V., de la Torre, R., Roquer, J., Dage, J. L., Zetterberg, H., Blennow, K., & Suárez‐Calvet, M.
- Affiliations
- King's College London (GB)
- Universitat Autònoma de Barcelona (ES)
- Universitat Pompeu Fabra (ES)
- Pasqual Maragall Foundation (ES)
- Hospital Del Mar (ES)
- Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy University of Gothenburg Sweden
- University of Gothenburg (SE)
- Universidade Federal do Rio Grande do Sul (BR)
- Eli Lilly (United States) (US)
- ADx NeuroSciences (BE)
- Janssen (United States) (US)
- University of Pittsburgh (US)
- IMIM (Hospital del Mar Medical Research Institute) Barcelona Spain
- Laboratori de Referència de Catalunya Barcelona Spain
- Cognitive Decline and Movement Disorders Unit Neurology Department Hospital del Mar Barcelona Spain
- Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Blennow, Kaj
- Suárez‐Calvet, Marc
- ORCID
- Ashton, Nicholas J.
- Puig‐Pijoan, Albert
- Milà‐Alomà, Marta
- Fernández‐Lebrero, Aida
- Kac, Przemysław R.
- Brum, Wagner S.
- Benedet, Andréa L.
- Lantero‐Rodriguez, Juan
- Day, Theresa A.
- Stoops, Erik
- Vanmechelen, Eugeen
- Triana‐Baltzer, Gallen
- Kolb, Hartmuth
- Ortiz‐Romero, Paula
- Karikari, Thomas K.
- Navalpotro‐Gómez, Irene
- Grau‐Rivera, Oriol
- Roquer, Jaume
- Zetterberg, Henrik
- Blennow, Kaj
- Suárez‐Calvet, Marc
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2022-11-12
- Volume
- 19
- Issue
- 5
- Pages
- 1913-1924
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC10762642
- OpenAlex
- W4308890634
- Cited by
- 230
- References
- 6
- Citations by year
- 2026: 41 · 2025: 82 · 2024: 70 · 2023: 36
- FWCI
- 30.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- IUScholarWorks (Indiana University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Alzheimer's Association (ADSF-21-831377-C, ADSF‐21‐831376‐C, -21-850325, #ADSF-21-831381-C, 100010434, 850325, 2019‐AARF‐644568, U24AG021886, -21- 831377-C, AARF-21-850325)
- Alzheimer's Drug Discovery Foundation (2016862, FO2017-0243, 201809, ADSF-21-831381-C, 2017-00915, #ALFGBG-715986, 201809–2016862, ADSF-21-831377-C, 860197, JPND2019-466-236, JPND2021-00694, 201809-2016615, #ADSF-21-831376-C, #RDAPB‐201809‐2016615, AF-742881)
- Eli Lilly and Company
- Biogen
- BrightFocus Foundation (AF-930627, A2020812F)
- Familjen Erling-Perssons Stiftelse (FO2019-0228, 860197)
- Gun och Bertil Stohnes Stiftelse
- Demensförbundet
- Stiftelsen för Gamla Tjänarinnor (860197, FO2019‐0228)
- EU Joint Programme – Neurodegenerative Disease Research (JPND 2021-00694, JPND2019-466-236)
- Ministerio de Ciencia, Innovación y Universidades (100010434, IJC2020-043417-I)
- European Commission (100010434, 847648, 948677, JPND2021‐00694, HORIZON2020, JPND2019‐466‐236, 860197, ID 100010434)
- Hjärnfonden (FO2017‑0243, FO2017, ALFGBG-715986, #FO2020-0240, FO2019‐0228, JPND2019-466-236)
- Vetenskapsrådet (2017-00915, (#ALFGBG-715986, 681712, 2018-, JPND2019-466-236, FO2017-0243, 2018-02532)
- Göteborgs Universitet
- Alzheimerfonden (#AF-930627, AF-742881)
- International Society for Neurochemistry
- Siemens Healthineers
- Julius Clinical
- UK Dementia Research Institute (#2017-00915)
- Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona (ID 100010434, 100010434)
- National Institutes of Health (RD005665, 100010434)
- Parkinsonfonden
- School of Medicine, Indiana University
- Instituto de Salud Carlos III (PI21/00194, PI19/00117, PI19/00155)
- National Institute on Aging (U01AG057195, R01AG068398, P30AG072976, U24AG021886)
- H2020 European Research Council (681712)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- phosphorylated tau, plasma biomarkers
- MeSH terms
- Alzheimer Disease, Enzyme-Linked Immunosorbent Assay, Humans, Immunoassay, Biomarkers, Amyloid beta-Peptides, tau Proteins, 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
