CoChat
Sign Up
Cited by 54Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis Research

Plasma p‐tau217 predicts in vivo brain pathology and cognition in autosomal dominant Alzheimer's disease

Open access
Aguillon, David, Langella, Stephanie, Chen, Yinghua, Sanchez, Justin S., Su, Yi, Vila‐Castelar, Clara, Vasquez, Daniel, Zetterberg, Henrik +16 more·2023·Alzheimer's & Dementia
DOI 10.1002/alz.12906PMC PMC10271963
Open this paper in CoChat — free accountOpen PDF

Abstract

Introduction: Plasma‐measured tau phosphorylated at threonine 217 (p‐tau217) is a potential non‐invasive biomarker of Alzheimer's disease (AD). We investigated whether plasma p‐tau217 predicts subsequent cognition and positron emission tomography (PET) markers of pathology in autosomal dominant AD. Methods: We analyzed baseline levels of plasma p‐tau217 and its associations with amyloid PET, tau PET, and word list delayed recall measured 7.61 years later in non‐demented age‐ and education‐matched presenilin‐1 E280A carriers (n = 24) and non‐carrier (n = 20) family members. Results: Carriers had higher plasma p‐tau217 levels than non‐carriers. Baseline plasma p‐tau217 was associated with subsequent amyloid and tau PET pathology levels and cognitive function. Discussion: Our findings suggest that plasma p‐tau217 predicts subsequent brain pathological burden and memory performance in presenilin‐1 E280A carriers. These results provide support for plasma p‐tau217 as a minimally invasive diagnostic and prognostic biomarker for AD, with potential utility in clinical practice and trials. Highlights: Non‐demented presenilin‐1 E280A carriers have higher plasma tau phosphorylated at threonine 217 (p‐tau217) than do age‐matched non‐carriers. Higher baseline p‐tau217 is associated with greater future amyloid positron emission tomography (PET) pathology burden. Higher baseline p‐tau217 is associated with greater future tau PET pathology burden. Higher baseline p‐tau217 is associated with worse future memory performance.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/alz.12906

Cites

8 of 8 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • In the Paisa kindred, plasma alterations such as elevated Aβ1-42, altered Aβ1-42/Aβ1-40 ratios, and increased p-tau217 appear before clinical symptom onset.

    “In the Paisa kindred, plasma alterations such as elevated amyloid beta (Aβ)1‐42, altered Aβ1‐42/Aβ1‐40 ratios, and increased tau phosphorylated at threonine 217 (p‐tau217) appear before clinical symptom onset. 16 , 17”

    From Plasma extracellular vesicles from <i>APOE3</i> Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease (2026) · cites this paper as [17]

    The Discussion reports higher plasma p-tau217 in PSEN1 E280A carriers than in non-carriers before cognitive impairment. The paper does not report presymptomatic elevations in plasma Aβ1-42 or altered plasma Aβ1-42/Aβ1-40 ratios; its amyloid findings concern brain PET measurements, not those plasma markers (Results, “Group differences in biomarkers at follow-up assessment”). (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

Flagged first, then by citations

Research works printed but not linked: 36

  1. [1]Chandra A, Valkimadi P, Pagano G, Cousins O, Dervenoulas G, Politis M. Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer’s disease and mild cognitive impairment. Hum Brain Mapp. 2019 Sep 14; 40(18): 5424– 42. 31520513 PMC6864887
  2. [2]Bjerke M, Engelborghs S. Cerebrospinal Fluid Biomarkers for Early and Differential Alzheimer’s Disease Diagnosis. J Alzheimers Dis JAD. 2018; 62(3): 1199– 209. 29562530 PMC5870045
  3. [3]Leuzy A, Cullen NC, Mattsson-Carlgren N, Hansson O. Current advances in plasma and cerebrospinal fluid biomarkers in Alzheimer’s disease. Curr Opin Neurol. 2021 Apr 1; 34(2): 266– 74. 33470669
  4. [4]Telser J, Risch L, Saely CH, Grossmann K, Werner P. P-tau217 in Alzheimer’s disease. Clin Chim Acta Int J Clin Chem. 2022 Jun 1; 531: 100– 11. 35341762
  5. [6]Wennström M, Janelidze S, Nilsson KPR, Netherlands Brain Bank, Serrano GE, Beach TG, Cellular localization of p-tau217 in brain and its association with p-tau217 plasma levels. Acta Neuropathol Commun. 2022 Jan 6; 10(1): 3. 34991721 PMC8734209
  6. [7]Palmqvist S, Janelidze S, Quiroz YT, Zetterberg H, Lopera F, Stomrud E, Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA. 2020 Aug 25; 324(8): 772– 81. 32722745 PMC7388060
  7. [8]Brickman AM, Manly JJ, Honig LS, Sanchez D, Reyes-Dumeyer D, Lantigua RA, Plasma p-tau181, p-tau217, and other blood-based Alzheimer’s disease biomarkers in a multi-ethnic, community study. Alzheimers Dement J Alzheimers Assoc. 2021 Aug; 17(8): 1353– 64. PMC8451860 33580742
  8. [9]Bayoumy S, Verberk IMW, den Dulk B, Hussainali Z, Zwan M, van der Flier WM, Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231. Alzheimers Res Ther. 2021 Dec 4; 13(1): 198. 34863295 PMC8645090
  9. [10]Cullen NC, Leuzy A, Janelidze S, Palmqvist S, Svenningsson AL, Stomrud E, Plasma biomarkers of Alzheimer’s disease improve prediction of cognitive decline in cognitively unimpaired elderly populations. Nat Commun. 2021 Jun 11; 12(1): 3555. 34117234 PMC8196018
  10. [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 Nov 2; 217(11): e20200861. 32725127 PMC7596823
  11. [12]Mattsson-Carlgren N, Janelidze S, Palmqvist S, Cullen N, Svenningsson AL, Strandberg O, Longitudinal plasma p-tau217 is increased in early stages of Alzheimer’s disease. Brain J Neurol. 2020 Dec 5; 143(11): 3234– 41. PMC7719022 33068398
  12. [13]Barthélemy NR, Li Y, Joseph-Mathurin N, Gordon BA, Hassenstab J, Benzinger TLS, A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease. Nat Med. 2020 Mar; 26(3): 398– 407. 32161412 PMC7309367
  13. [14]Pichet Binette A, Palmqvist S, Bali D, Farrar G, Buckley CJ, Wolk DA, Combining plasma phospho-tau and accessible measures to evaluate progression to Alzheimer’s dementia in mild cognitive impairment patients. Alzheimers Res Ther. 2022 Mar 29; 14(1): 46. 35351181 PMC8966264
  14. [15]Janelidze S, Berron D, Smith R, Strandberg O, Proctor NK, Dage JL, Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease. JAMA Neurol. 2021 Feb 1; 78(2): 149– 56. 33165506 PMC7653537
  15. [17]Mattsson-Carlgren N, Janelidze S, Bateman RJ, Smith R, Stomrud E, Serrano GE, Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau. EMBO Mol Med. 2021 Jun 7; 13(6): e14022. 33949133 PMC8185545
  16. [18]Leuzy A, Smith R, Cullen NC, Strandberg O, Vogel JW, Binette AP, Biomarker-Based Prediction of Longitudinal Tau Positron Emission Tomography in Alzheimer Disease. JAMA Neurol. 2022 Feb 1; 79(2): 149– 58. 34928318 PMC8689441
  17. [19]Reiman EM, Langbaum JBS, Fleisher AS, Caselli RJ, Chen K, Ayutyanont N, Alzheimer’s Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments. J Alzheimers Dis JAD. 2011; 26 Suppl 3: 321– 9. 21971471 PMC3343739
  18. [20]Fuller JT, Cronin-Golomb A, Gatchel JR, Norton DJ, Guzmán-Vélez E, Jacobs HIL, Biological and Cognitive Markers of Presenilin1 E280A Autosomal Dominant Alzheimer’s Disease: A Comprehensive Review of the Colombian Kindred. J Prev Alzheimers Dis. 2019; 6(2): 112– 20. 30756118 PMC6925534
  19. [23]Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov; 12(3): 189– 98. 1202204
  20. [24]Reisberg B Functional assessment staging (FAST). Psychopharmacol Bull. 1988; 24(4): 653– 9. 3249767
  21. [25]Aguirre-Acevedo DC, Gómez RD, Moreno S, Henao-Arboleda E, Motta M, Muñoz C, [Validity and reliability of the CERAD-Col neuropsychological battery]. Rev Neurol. 2007 Dec 1; 45(11): 655– 60. 18050096
  22. [27]Logan J, Fowler JS, Volkow ND, Wolf AP, Dewey SL, Schlyer DJ, Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(−)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 1990 Sep; 10(5): 740– 7. 2384545
  23. [28]Amariglio RE, Mormino EC, Pietras AC, Marshall GA, Vannini P, Johnson KA, Subjective cognitive concerns, amyloid-β, and neurodegeneration in clinically normal elderly. Neurology. 2015 Jul 7; 85(1): 56– 62. 26048028 PMC4501939
  24. [29]Johnson KA, Schultz A, Betensky RA, Becker JA, Sepulcre J, Rentz D, Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol. 2016 Jan; 79(1): 110– 9. 26505746 PMC4738026
  25. [31]Sanchez JS, Hanseeuw BJ, Lopera F, Sperling RA, Baena A, Bocanegra Y, Longitudinal amyloid and tau accumulation in autosomal dominant Alzheimer’s disease: findings from the Colombia-Boston (COLBOS) biomarker study. Alzheimers Res Ther. 2021 Jan 15; 13(1): 27. 33451357 PMC7811244
  26. [32]Greve DN, Svarer C, Fisher PM, Feng L, Hansen AE, Baare W, Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data. NeuroImage. 2014 May 15; 92: 225– 36. 24361666 PMC4008670
  27. [33]Lendon CL, Martinez A, Behrens IM, Kosik KS, Madrigal L, Norton J, E280A PS-1 mutation causes Alzheimer’s disease but age of onset is not modified by ApoE alleles. Hum Mutat. 1997; 10(3): 186– 95. 9298817
  28. [34]Janelidze S, Palmqvist S, Leuzy A, Stomrud E, Verberk IMW, Zetterberg H, Detecting amyloid positivity in early Alzheimer’s disease using combinations of plasma Aβ42/Aβ40 and p-tau. Alzheimers Dement J Alzheimers Assoc. 2022 Feb; 18(2): 283– 93. 34151519
  29. [35]Ossenkoppele R, Reimand J, Smith R, Leuzy A, Strandberg O, Palmqvist S, Tau PET correlates with different Alzheimer’s disease-related features compared to CSF and plasma p-tau biomarkers. EMBO Mol Med. 2021 Aug 9; 13(8): e14398. 34254442 PMC8350902
  30. [36]Guzmán-Vélez E, Diez I, Schoemaker D, Pardilla-Delgado E, Vila-Castelar C, Fox-Fuller JT, Amyloid-β and tau pathologies relate to distinctive brain dysconnectomics in preclinical autosomal-dominant Alzheimer’s disease. Proc Natl Acad Sci U S A. 2022 Apr 12; 119(15): e2113641119. 35380901 PMC9169643
  31. [38]Moscoso A, Grothe MJ, Ashton NJ, Karikari TK, Lantero Rodríguez J, Snellman A, Longitudinal Associations of Blood Phosphorylated Tau181 and Neurofilament Light Chain With Neurodegeneration in Alzheimer Disease. JAMA Neurol. 2021 Apr 1; 78(4): 396– 406. 33427873 PMC7802009
  32. [39]Tissot C, L Benedet A, Therriault J, Pascoal TA, Lussier FZ, Saha-Chaudhuri P, Plasma pTau181 predicts cortical brain atrophy in aging and Alzheimer’s disease. Alzheimers Res Ther. 2021 Mar 29; 13(1): 69. PMC8008680 33781319
  33. [40]Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL, 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 May; 19(5): 422– 33. 32333900
  34. [41]Moscoso A, Grothe MJ, Ashton NJ, Karikari TK, Rodriguez JL, Snellman A, Time course of phosphorylated-tau181 in blood across the Alzheimer’s disease spectrum. Brain J Neurol. 2021 Feb 12; 144(1): 325– 39. PMC7880671 33257949
  35. [42]Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol (Berl). 2014 Dec; 128(6): 755– 66. 25348064 PMC4257842
  36. [43]Morris JC, Weiner M, Xiong C, Beckett L, Coble D, Saito N, Autosomal dominant and sporadic late onset Alzheimer disease share a common in vivo pathophysiology. Brain J Neurol. 2022 May 17; awac181. PMC9989348 35580594

Cited by

Sorted by citations

Authors
Aguillon, D., Langella, S., Chen, Y., Sanchez, J. S., Su, Y., Vila‐Castelar, C., Vasquez, D., Zetterberg, H., Hansson, O., Dage, J. L., Janelidze, S., Chen, K., Fox‐Fuller, J. T., Aduen, P., Martinez, J. E., Garcia, G., Baena, A., Guzman, C., Johnson, K. A., Sperling, R. A., Blennow, K., Reiman, E. M., Lopera, F., & Quiroz, Y. T.
Affiliations
  • Universidad de Antioquia (CO)
  • Harvard University (US)
  • Banner Alzheimer’s Institute (US)
  • Grupo de Neurociencias de Antioquia, Facultad de Medicina Universidad de Antioquia Medellin Colombia
  • Sahlgrenska University Hospital (SE)
  • Lund University (SE)
  • Indiana University School of Medicine (US)
  • Skåne University Hospital (SE)
  • Boston University (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Quiroz, Yakeel T.
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2022-12-26
Volume
19
Issue
6
Pages
2585-2594
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.12906
PMC
PMC10271963
OpenAlex
W4312212024
Cited by
54
References
8
Citations by year
2026: 11 · 2025: 18 · 2024: 13 · 2023: 11
FWCI
6.84
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Alzheimer s & Dementia (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Alzheimer's Association (ADSF-21-831377-C, ZEN-21-848495, ADSF‐21‐831376‐C, #ADSF-21-831381-C, 2021 Zenith Award, -21- 831377-C)
  • Alzheimer's Drug Discovery Foundation (2016862, FO2017-0243, 201809, ADSF-21-831381-C, 2017-00915, UKDRI-1003, #ALFGBG-715986, ZEN-21-848495, 201809–2016862, ADSF-21-831377-C, 860197, JPND2019-466-236, JPND2021-00694, 201809-2016615, #ADSF-21-831376-C, #RDAPB‐201809‐2016615)
  • Eli Lilly and Company
  • Massachusetts General Hospital
  • Biogen
  • BrightFocus Foundation
  • Familjen Erling-Perssons Stiftelse (FO2019-0228, 860197)
  • Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS) (111565741185)
  • Stiftelsen för Gamla Tjänarinnor (860197, FO2019‐0228)
  • EU Joint Programme – Neurodegenerative Disease Research (JPND 2021-00694, JPND2019-466-236)
  • Australian Government
  • European Commission (101,053,962, JPND2021‐00694, HORIZON2020, ALFGBG-71320, JPND2019‐466‐236, 860197)
  • Lunds Universitet
  • Hjärnfonden (ALZ2022-0006), FO2021-0293, FO2017‑0243, FO2017, ALFGBG-715986, FO2019‐0228, #ALFGBG-965240, JPND2019-466-236)
  • Knut och Alice Wallenbergs Stiftelse (681712, 2017‐0383)
  • Vetenskapsrådet (ALFGBG-965240, ALZ2022-0006, #101053962, 2017-00915, 2016-00906, (#ALFGBG-715986, ALFGBG‐71320, 681712, FO2021-0293, 2018-, JPND2019-466-236, 2017-00383, FO2017-0243, 2018-02532)
  • Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse (2020-O000028, 2020-0314, FO2017-0243)
  • NOMIS Stiftung
  • Skånes universitetssjukhus (2020-O000028)
  • Marcus och Amalia Wallenbergs minnesfond (2015.0125)
  • UK Dementia Research Institute (#2017-00915, UKDRI‐ 1003)
  • National Institutes of Health (ZEN-21- 848495, AG19610)
  • Genentech
  • Parkinsonfonden (1280/20)
  • Avid Radiopharmaceuticals
  • National Institute on Aging (P30-AG-19610, AG-19610, R01AG068398, R01AG055444, F31AG062158, AG031581, R01AG031581, P30AG019610, R01AG054671, RF1AG077627, P30AG072980)
  • National Institute of Biomedical Imaging and Bioengineering
  • 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 › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
plasma p-tau217, tau phosphorylation
MeSH terms
Alzheimer Disease, Amyloid, Brain, Cognition, Humans, Biomarkers, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Presenilin-1, Amyloidogenic Proteins

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