24 januari 2024: zie enkele artikelen via deze search met zoekwoord Alzheimer op onze website.

24 januari 2024: Bron: JAMA Neurol. Published online January 22, 2024.

Een eenvoudige bloedtest blijkt tot 96 procent nauwkeurig de ziekte van Alzheimer - dementie te kunnen aantonen door het meten van verhoogde niveaus van beta-amyloid en tot 97 procent bij het identificeren van p-tau217. Deze twee eiwitten veroorzaken de ziekte van Alzheimer - dementie.

De bloedtest kan ook al jaren voordat de ziekte zich manifesteert aantonen dat de ziekte zich gaat voordoen. Verder blijkt de bloedtest een patiëntvriendelijker en goedkoper alternatief voor andere diagnosetechnieken van dementie.  

De ziekte van Alzheimer - dementie is een aandoening die naarmate de ziekte erger wordt iemand steeds meer moeite met dagelijkse vaardigheden krijgt en wordt tot nu toe gezien als ongeneeslijk. Wel kan met vooral een gezonde leefstijl de progressie van de ziekte afgeremd worden, zie enkele artikelen via deze search met zoekwoord Alzheimer op onze website.

Uit een recent gepubliceerde studie bleek dat de p-tau217-immunoassay vergelijkbare nauwkeurigheid vertoonde als biomarkers voor hersenvocht bij het identificeren van abnormale amyloïde β (Aβ) en tau-pathologieën.
In drie verschillende onafhankelijk van elkaar uitgevoerde studies voor het detecteren van abnormale Aβ-pathologie waren de resultaten van de bloedtest consistent in alle drie de studiegroepen;
Over een periode van acht jaar vond de grootste verandering in p-tau217 plaats bij individuen die positief waren voor zowel Aβ als tau.

Het originele studierapport is gratis in te zien. Hier het abstract van deze studie:
January 22, 2024

Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology

Nicholas J. Ashton, PhD1,2,3,4; Wagner S. Brum1,5; Guglielmo Di Molfetta, MSc1; et alAndrea L. Benedet, PhD1; Burak Arslan, MD1; Erin Jonaitis, PhD6,7,8; Rebecca E. Langhough, PhD6,7,8; Karly Cody, PhD7; Rachael Wilson, PhD7,8; Cynthia M. Carlsson, PhD6,7,8,9; Eugeen Vanmechelen, PhD10; Laia Montoliu-Gaya, PhD1; Juan Lantero-Rodriguez, PhD1; Nesrine Rahmouni, MSc11,12; Cecile Tissot, PhD11,12; Jenna Stevenson, PhD11,12; Stijn Servaes, PhD11,12; Joseph Therriault, PhD11,12; Tharick Pascoal, MD, PhD13,14; Alberto Lleó, MD, PhD15,16; Daniel Alcolea, MD, PhD15,16; Juan Fortea, MD, PhD15,16; Pedro Rosa-Neto, MD, PhD11,12; Sterling Johnson, MD, PhD6,7; Andreas Jeromin, PhD17; Kaj Blennow, MD, PhD1,18; Henrik Zetterberg, MD, PhD1,7,18,19,20,21
Author Affiliations Article Information
JAMA Neurol. Published online January 22, 2024. doi:10.1001/jamaneurol.2023.5319
Key Points

Question  What are the capabilities of a commercially available plasma phosphorylated tau 217 (p-tau217) immunoassay to identify Alzheimer disease pathophysiology?

Findings  This cohort study found that the p-tau217 immunoassay showed similar accuracies to cerebrospinal fluid biomarkers in identifying abnormal amyloid β (Aβ) and tau pathologies. A 3-range reference for detecting abnormal Aβ pathology was consistent across 3 cohorts; over 8 years, the largest change of p-tau217 was in individuals positive for both Aβ and tau.

Meaning  The wider availability of high-performing assays may expedite the use of blood biomarkers in clinical settings and benefit the research community.

Abstract

Importance  Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of p-tau217 tests for research and clinical use has been limited. Expanding access to this highly accurate AD biomarker is crucial for wider evaluation and implementation of AD blood tests.

Objective  To determine the utility of a novel and commercially available immunoassay for plasma p-tau217 to detect AD pathology and evaluate reference ranges for abnormal amyloid β (Aβ) and longitudinal change across 3 selected cohorts.

Design, Setting, and Participants  This cohort study examined data from 3 single-center observational cohorts: cross-sectional and longitudinal data from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (visits October 2017–August 2021) and Wisconsin Registry for Alzheimer’s Prevention (WRAP) cohort (visits February 2007–November 2020) and cross-sectional data from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort (baseline visits March 2009–November 2021). Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023.

Exposures  Magnetic resonance imaging, Aβ positron emission tomography (PET), tau PET, cerebrospinal fluid (CSF) biomarkers (Aβ42/40 and p-tau immunoassays), and plasma p-tau217 (ALZpath pTau217 assay).

Main Outcomes and Measures  Accuracy of plasma p-tau217 in detecting abnormal amyloid and tau pathology, longitudinal p-tau217 change according to baseline pathology status.

Results  The study included 786 participants (mean age, 66.3 [9.7] years; 504 females [64.1%] and 282 males [35.9%]). High accuracy was observed in identifying elevated Aβ (area under the curve , 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signal. The detection of abnormal Aβ pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80%. Longitudinally, plasma p-tau217 values showed an annual increase only in Aβ-positive individuals, with the highest increase observed in those with tau positivity.

Conclusions and Relevance  This study found that a commercially available plasma p-tau217 immunoassay accurately identified biological AD, comparable with results using CSF biomarkers, with reproducible cut-offs across cohorts. It detected longitudinal changes, including at the preclinical stage.

Article Information

Accepted for Publication: November 10, 2023.

Published Online: January 22, 2024. doi:10.1001/jamaneurol.2023.5319

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2024 Ashton NJ et al. JAMA Neurology.

Corresponding Author: Nicholas J. Ashton, PhD, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Mölndal Hospital, Hus V3, 43180 Mölndal, Sweden (nicholas.ashton@gu.se).

Author Contributions: Dr Ashton had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Ashton and Mr Brum contributed equally as co–first authors.

Concept and design: Ashton, Brum, Benedet, Vanmechelen, Montoliu-Gaya, Servaes, Therriault, Pascoal, Johnson, Blennow, Zetterberg.

Acquisition, analysis, or interpretation of data: Ashton, Brum, Di Molfetta, Benedet, Arslan, Jonaitis, Langhough, Cody, Wilson, Carlsson, Montoliu-Gaya, Lantero-Rodriguez, Rahmouni, Tissot, Stevenson, Therriault, Pascoal, Lleó, Alcolea, Fortea, Rosa-Neto, Johnson, Jeromin, Blennow, Zetterberg.

Drafting of the manuscript: Ashton, Brum, Arslan, Johnson.

Critical review of the manuscript for important intellectual content: Ashton, Brum, Di Molfetta, Benedet, Jonaitis, Langhough, Cody, Wilson, Carlsson, Vanmechelen, Montoliu-Gaya, Lantero-Rodriguez, Rahmouni, Tissot, Stevenson, Servaes, Therriault, Pascoal, Lleó, Alcolea, Fortea, Rosa-Neto, Johnson, Jeromin, Blennow, Zetterberg.

Statistical analysis: Ashton, Brum, Jonaitis, Therriault.

Obtained funding: Tissot, Fortea, Rosa-Neto, Johnson, Zetterberg.

Administrative, technical, or material support: Ashton, Benedet, Jonaitis, Cody, Wilson, Carlsson, Vanmechelen, Montoliu-Gaya, Rahmouni, Tissot, Stevenson, Servaes, Therriault, Lleó, Fortea, Rosa-Neto, Jeromin, Zetterberg.

Supervision: Ashton, Fortea, Blennow.

Additional Contributions: We thank Jeroen Vanbrabant, PhD, and Erik Stoops, PhD, from ADx Neuroscience, now Fujirebio, and the accelerator lab at Quanterix, for the initial prototyping of the ALZpath pTau217 assay.

References
1.
Hansson  O.  Biomarkers for neurodegenerative diseases.   Nat Med. 2021;27(6):954-963. doi:10.1038/s41591-021-01382-xPubMedGoogle ScholarCrossref
2.
Hansson  O, Blennow  K, Zetterberg  H, Dage  J.  Blood biomarkers for Alzheimer’s disease in clinical practice and trials.   Nat Aging. 2023;3(5):506-519. doi:10.1038/s43587-023-00403-3PubMedGoogle ScholarCrossref
3.
Ashton  NJ, Janelidze  S, Al Khleifat  A,  et al.  A multicentre validation study of the diagnostic value of plasma neurofilament light.   Nat Commun. 2021;12(1):3400. doi:10.1038/s41467-021-23620-zPubMedGoogle ScholarCrossref
4.
Benedet  AL, Milà-Alomà  M, Vrillon  A,  et al; Translational Biomarkers in Aging and Dementia (TRIAD) study, Alzheimer’s and Families (ALFA) study, and BioCogBank Paris Lariboisière cohort.  Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the Alzheimer disease continuum.   JAMA Neurol. 2021;78(12):1471-1483. doi:10.1001/jamaneurol.2021.3671
ArticlePubMedGoogle ScholarCrossref
5.
Hampel  H, Hardy  J, Blennow  K,  et al.  The amyloid-β pathway in Alzheimer’s disease.   Mol Psychiatry. 2021;26(10):5481-5503. doi:10.1038/s41380-021-01249-0PubMedGoogle ScholarCrossref
6.
Schindler  SE, Bollinger  JG, Ovod  V,  et al.  High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis.   Neurology. 2019;93(17):e1647-e1659. doi:10.1212/WNL.0000000000008081PubMedGoogle ScholarCrossref
7.
Karikari  TK, Ashton  NJ, Brinkmalm  G,  et al.  Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility.   Nat Rev Neurol. 2022;18(7):400-418. doi:10.1038/s41582-022-00665-2PubMedGoogle ScholarCrossref
8.
Benedet  AL, Brum  WS, Hansson  O,  et al; Alzheimer’s Disease Neuroimaging Initiative.  The accuracy and robustness of plasma biomarker models for amyloid PET positivity.   Alzheimers Res Ther. 2022;14(1):26. doi:10.1186/s13195-021-00942-0PubMedGoogle ScholarCrossref
9.
Cullen  NC, Janelidze  S, Mattsson-Carlgren  N,  et al.  Test-retest variability of plasma biomarkers in Alzheimer’s disease and its effects on clinical prediction models.   Alzheimers Dement. Published online June 14, 2022. doi:10.1002/alz.12706PubMedGoogle ScholarCrossref
10.
Ashton  NJ, Puig-Pijoan  A, Mila-Aloma  M,  et al.  Plasma and CSF biomarkers in a memory clinic: head-to-head comparison of phosphorylated tau immunoassays.   Alzheimers Dement. 2023;19(5):1913-1924. doi:10.1002/alz.12841PubMedGoogle ScholarCrossref
11.
O’Connor  A, Karikari  TK, Poole  T,  et al.  Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer’s disease: a longitudinal cohort study.   Mol Psychiatry. 2021;26(10):5967-5976. doi:10.1038/s41380-020-0838-xPubMedGoogle ScholarCrossref
12.
Lleó  A, Zetterberg  H, Pegueroles  J,  et al.  Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer’s disease in adults with Down syndrome.   Nat Commun. 2021;12(1):4304. doi:10.1038/s41467-021-24319-xPubMedGoogle ScholarCrossref
13.
Janelidze  S, Christian  BT, Price  J,  et al.  Detection of brain tau pathology in Down syndrome using plasma biomarkers.   JAMA Neurol. 2022;79(8):797-807. doi:10.1001/jamaneurol.2022.1740
ArticlePubMedGoogle ScholarCrossref
14.
Fortea  J, Zaman  SH, Hartley  S, Rafii  MS, Head  E, Carmona-Iragui  M.  Alzheimer’s disease associated with Down syndrome: a genetic form of dementia.   Lancet Neurol. 2021;20(11):930-942. doi:10.1016/S1474-4422(21)00245-3PubMedGoogle ScholarCrossref
15.
Mattsson-Carlgren  N, Janelidze  S, Bateman  RJ,  et al.  Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau.   EMBO Mol Med. 2021;13(6):e14022. doi:10.15252/emmm.202114022PubMedGoogle ScholarCrossref
16.
Salvadó  G, Ossenkoppele  R, Ashton  NJ,  et al.  Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads.   EMBO Mol Med. 2023;15(5):e17123. doi:10.15252/emmm.202217123PubMedGoogle ScholarCrossref
17.
Lantero Rodriguez  J, Karikari  TK, Suárez-Calvet  M,  et al.  Plasma p-tau181 accurately predicts Alzheimer’s disease pathology at least 8 years prior to post-mortem and improves the clinical characterisation of cognitive decline.   Acta Neuropathol. 2020;140(3):267-278. doi:10.1007/s00401-020-02195-xPubMedGoogle ScholarCrossref
18.
Ashton  NJ, Pascoal  TA, Karikari  TK,  et al.  Plasma p-tau231: a new biomarker for incipient Alzheimer’s disease pathology.   Acta Neuropathol. 2021;141(5):709-724. doi:10.1007/s00401-021-02275-6PubMedGoogle ScholarCrossref
19.
Palmqvist  S, Janelidze  S, Quiroz  YT,  et al.  Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders.   JAMA. 2020;324(8):772-781. doi:10.1001/jama.2020.12134
ArticlePubMedGoogle ScholarCrossref
20.
Janelidze  S, Mattsson  N, Palmqvist  S,  et al.  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/s41591-020-0755-1PubMedGoogle ScholarCrossref
21.
Montoliu-Gaya  L, Benedet  AL, Tissot  C,  et al.  Mass spectrometric simultaneous quantification of tau species in plasma shows differential associations with amyloid and tau pathologies.   Nat Aging. 2023;3(6):661-669. doi:10.1038/s43587-023-00405-1PubMedGoogle ScholarCrossref
22.
Janelidze  S, Bali  D, Ashton  NJ,  et al.  Head-to-head comparison of 10 plasma phospho-tau assays in prodromal Alzheimer’s disease.   Brain. 2023;146(4):1592-1601. doi:10.1093/brain/awac333PubMedGoogle ScholarCrossref
23.
Thijssen  EH, La Joie  R, Strom  A,  et al; Advancing Research and Treatment for Frontotemporal Lobar Degeneration investigators.  Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer’s disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study.   Lancet Neurol. 2021;20(9):739-752. doi:10.1016/S1474-4422(21)00214-3PubMedGoogle ScholarCrossref
24.
Ashton  NJ, Janelidze  S, Mattsson-Carlgren  N,  et al.  Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring.   Nat Med. 2022;28(12):2555-2562. doi:10.1038/s41591-022-02074-wPubMedGoogle ScholarCrossref
25.
Jonaitis  EM, Janelidze  S, Cody  KA,  et al.  Plasma phosphorylated tau 217 in preclinical Alzheimer’s disease.   Brain Commun. 2023;5(2):fcad057. doi:10.1093/braincomms/fcad057PubMedGoogle ScholarCrossref
26.
Johnson  SC, Koscik  RL, Jonaitis  EM,  et al.  The Wisconsin Registry for Alzheimer’s Prevention: a review of findings and current directions.   Alzheimers Dement (Amst). 2017;10:130-142. doi:10.1016/j.dadm.2017.11.007PubMedGoogle ScholarCrossref
27.
Alcolea  D, Clarimón  J, Carmona-Iragui  M,  et al.  The Sant Pau Initiative on Neurodegeneration (SPIN) cohort: a data set for biomarker discovery and validation in neurodegenerative disorders.   Alzheimers Dement (N Y). 2019;5:597-609. doi:10.1016/j.trci.2019.09.005PubMedGoogle ScholarCrossref
28.
Cselényi  Z, Jönhagen  ME, Forsberg  A,  et al.  Clinical validation of 18F-AZD4694, an amyloid-β-specific PET radioligand.   J Nucl Med. 2012;53(3):415-424. doi:10.2967/jnumed.111.094029PubMedGoogle ScholarCrossref
29.
Pascoal  TA, Shin  M, Kang  MS,  et al.  In vivo quantification of neurofibrillary tangles with [18F]MK-6240.   Alzheimers Res Ther. 2018;10(1):74. doi:10.1186/s13195-018-0402-yPubMedGoogle ScholarCrossref
30.
Johnson  SC, Christian  BT, Okonkwo  OC,  et al.  Amyloid burden and neural function in people at risk for Alzheimer’s disease.   Neurobiol Aging. 2014;35(3):576-584. doi:10.1016/j.neurobiolaging.2013.09.028PubMedGoogle ScholarCrossref
31.
Betthauser  TJ, Koscik  RL, Jonaitis  EM,  et al.  Amyloid and tau imaging biomarkers explain cognitive decline from late middle-age.   Brain. 2020;143(1):320-335. doi:10.1093/brain/awz378PubMedGoogle ScholarCrossref
32.
Betthauser  TJ, Cody  KA, Zammit  MD,  et al.  In vivo characterization and quantification of neurofibrillary tau PET radioligand 18F-MK-6240 in humans from Alzheimer disease dementia to young controls.   J Nucl Med. 2019;60(1):93-99. doi:10.2967/jnumed.118.209650PubMedGoogle ScholarCrossref
33.
Ashton  NJ, Benedet  AL, Pascoal  TA,  et al.  Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer’s disease.   EBioMedicine. 2022;76:103836. doi:10.1016/j.ebiom.2022.103836PubMedGoogle ScholarCrossref
34.
Therriault  J, Pascoal  TA, Benedet  AL,  et al.  Frequency of biologically defined Alzheimer disease in relation to age, sex, APOE ε4, and cognitive impairment.   Neurology. 2021;96(7):e975-e985. doi:10.1212/WNL.0000000000011416PubMedGoogle ScholarCrossref
35.
Therriault  J, Benedet  AL, Pascoal  TA,  et al.  Determining amyloid-β positivity using 18F-AZD4694 PET imaging.   J Nucl Med. 2021;62(2):247-252. doi:10.2967/jnumed.120.245209PubMedGoogle ScholarCrossref
36.
Alcolea  D, Pegueroles  J, Muñoz  L,  et al.  Agreement of amyloid PET and CSF biomarkers for Alzheimer’s disease on Lumipulse.   Ann Clin Transl Neurol. 2019;6(9):1815-1824. doi:10.1002/acn3.50873PubMedGoogle ScholarCrossref
37.
Van Hulle  C, Jonaitis  EM, Betthauser  TJ,  et al.  An examination of a novel multipanel of CSF biomarkers in the Alzheimer’s disease clinical and pathological continuum.   Alzheimers Dement. 2021;17(3):431-445. doi:10.1002/alz.12204PubMedGoogle ScholarCrossref
38.
Jani  D, Allinson  J, Berisha  F,  et al.  Recommendations for use and fit-for-purpose validation of biomarker multiplex ligand binding assays in drug development.   AAPS J. 2016;18(1):1-14. doi:10.1208/s12248-015-9820-yPubMedGoogle ScholarCrossref
39.
Hansson  O, Edelmayer  RM, Boxer  AL,  et al.  The Alzheimer’s Association appropriate use recommendations for blood biomarkers in Alzheimer’s disease.   Alzheimers Dement. 2022;18(12):2669-2686. doi:10.1002/alz.12756PubMedGoogle ScholarCrossref
40.
Rothman  KJ.  No adjustments are needed for multiple comparisons.   Epidemiology. 1990;1(1):43-46. doi:10.1097/00001648-199001000-00010PubMedGoogle ScholarCrossref
41.
Brum  WS, Cullen  NC, Janelidze  S,  et al.  A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases.   Nat Aging. 2023;3(9):1079-1090. doi:10.1038/s43587-023-00471-5PubMedGoogle ScholarCrossref
42.
Jansen  WJ, Janssen  O, Tijms  BM,  et al; Amyloid Biomarker Study Group.  Prevalence estimates of amyloid abnormality across the Alzheimer disease clinical spectrum.   JAMA Neurol. 2022;79(3):228-243. doi:10.1001/jamaneurol.2021.5216
ArticlePubMedGoogle ScholarCrossref
43.
Barthélemy  NR, Saef  B, Li  Y,  et al.  CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer’s disease.   Nat Aging. 2023;3(4):391-401. doi:10.1038/s43587-023-00380-7PubMedGoogle ScholarCrossref
44.
Lilly Investors. Lilly’s donanemab significantly slowed cognitive and functional decline in phase 3 study of early Alzheimer’s disease. Accessed June 18, 2023. https://investor.lilly.com/news-releases/news-release-details/lillys-donanemab-significantly-slowed-cognitive-and-functional
45.
Mintun  MA, Wessels  AM, Sims  JR.  Donanemab in early Alzheimer’s disease.  .  N Engl J Med. 2021;385(7):667. doi:10.1056/NEJMc2109455PubMedGoogle ScholarCrossref
46.
Vecchio  TJ.  Predictive value of a single diagnostic test in unselected populations.   N Engl J Med. 1966;274(21):1171-1173. doi:10.1056/NEJM196605262742104PubMedGoogle ScholarCrossref
47.
Mielke  MM, Dage  JL, Frank  RD,  et al.  Performance of plasma phosphorylated tau 181 and 217 in the community.   Nat Med. 2022;28(7):1398-1405. doi:10.1038/s41591-022-01822-2PubMedGoogle ScholarCrossref
48.
Mattsson-Carlgren  N, Leuzy  A, Janelidze  S,  et al.  The implications of different approaches to define AT(N) in Alzheimer disease.   Neurology. 2020;94(21):e2233-e2244. doi:10.1212/WNL.0000000000009485PubMedGoogle ScholarCrossref

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