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phosphorylated tau(Thr)217 in serum/plasma (plasma ptau217)

Reference interval: - plasma p-tau217: - normal < 0.159 ng/L - gray zone is 0.159-0.219 ng/L - abnormal > 0.219 ng/L Clinical significance: - plasma phosphorylated-tau217 (p-tau217) or plasma phosphorylated-tau181 (p-tau181) able to discriminate Alzheimer disease from other neurodegenerative diseases [2,12] - distinguishes from frontotemporal dementia [9] - longitudinal increase in plasma phosphorylated-tau217 may predict development of Alzheimer's disease[4] - plasma p-tau217 accurately identifies tau pathological brain changes in Down syndrome [10] - plasma p-tau217 levels are increased in early preclinical stages of AD when insoluble tau aggregates are not yet detectable by tau-PET [6,8] - preoperative plasma tau-p217 & plasma tau-p181 are associated with postoperative delirium, with plasma tau-p217 the stronger indicator [11] - plasma P-tau217 predicts cognitive decline in patients with preclinical AD [13] - plasma p-tau217 outperforms plasma p-tau181 & plasma p-tau231 & other plasma biomarkers of Alzheimer's disease in identifying which patients may benefit from an anti-beta-amyloid anti-Alzheimer monoclonal antibody [15] - plasma p-tau217 is strongly associated with amyloid-beta positivity - plasma p-tau217 classified into 3 categories, normal, gray zone, abnormal - gray zone is defined by a low cutoff of 0.159 ng/L & high cutoff of 0.219 ng/L - gray zone plasma p-tau217 is associated with likelihood of benefit from anti-beta-amyloid anti-Alzheimer monoclonal antibody, with sensitivity of 94% & specificity of 86% [15] - plasma p-tau217 may obviate the need for CSF testing or amyloid PET [15] - plasma p-tau217 immunoassay with similar accuracies to CSF biomarkers in identifying abnormal beta-amyloid & tau pathology [18] Method: - ELISA & other methods using polyclonal antibody [17] -

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phosphorylated tau217 in dried blood spot

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phosphorylated tau in serum/plasma

References

  1. Thijssen EH, La Joie R, Wolf A et al Diagnostic value of plasma phosphorylated tau181 in Alzheimer's disease and frontotemporal lobar degeneration. Nature Medicine 2020. March 2 PMID: 32123386 https://www.nature.com/articles/s41591-020-0762-2
  2. Palmqvist S, Janelidze S, Quiroz YT et al Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA. Published online July 28, 2020 PMID: 32722745 https://jamanetwork.com/journals/jama/fullarticle/2768841
  3. Barthelemy NR, Horie K, Sato C Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer's disease. J Exp Med (2020) 217 (11): e20200861 PMID: 32725127 https://rupress.org/jem/article/217/11/e20200861/151982/Blood-plasma-phosphorylated-tau-isoforms-track-CNS
  4. Mattsson-Carlgren N et al. Longitudinal plasma p-tau217 is increased in early stages of Alzheimer's disease. Brain 2020 Dec 5; 143:3234. PMID: 33068398 Free PMC article https://academic.oup.com/brain/article/143/11/3234/5929275
  5. George J Alzheimer's Blood Test Predicts Pathology - -tau181: "an important advance that could transform the diagnosis of Alzheimer's disease" MedPage Today January 6, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/90555 - Karikari TK, Pascoal TA, Ashton NJ et al 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):422-433. PMID: 32333900 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30071-5/fulltext - Karikari TK, Benedet AL, Ashton NJ et al Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer's Disease Neuroimaging Initiative. Mol Psychiatry. 2020 Oct 26. PMID: 33106600
  6. Janelidze S, Berron D, Smith R et al Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease. JAMA Neurol. 2021;78(2):149-156 PMID: 33165506 PMCID: PMC7653537 Free PMC article https://jamanetwork.com/journals/jamaneurology/fullarticle/2772866
  7. Largent EA, Wexler A, Karlawish J The Future Is P-Tau - Anticipating Direct-to-Consumer Alzheimer Disease Blood Tests. JAMA Neurol. 2021;78(4):379-380 PMID: 33393982 https://jamanetwork.com/journals/jamaneurology/fullarticle/2774173
  8. Pereira JB et al. Plasma markers predict changes in amyloid, tau, atrophy and cognition in non-demented subjects. Brain 2021 Jun 2; [e-pub]. PMID: 34077494 https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awab163/6291241
  9. George J Blood Test Discerns Alzheimer's From Other Dementia With High Accuracy. Plasma p-tau moves another step closer to clinical use. MedPage Today August 23, 2021 https://www.medpagetoday.com/neurology/alzheimersdisease/94177 - Thijssen EH, La Joie R, Strom A et al 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 PMID: 34418401 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00214-3/fulltext - Parnetti L, Di Filippo M, Gaetani L et al A blood test for Alzheimer's disease: a step forward. Lancet Neurol 2021. PMID: 34418386 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00254-4/fulltext - Thijssen EH, La Joie R, Wolf A et al Diagnostic value of plasma phosphorylated tau181 in Alzheimer's disease and frontotemporal lobar degeneration. Nature Medicine 2020. March 2 PMID: 32123386 https://www.nature.com/articles/s41591-020-0762-2
  10. Janelidze S, Christian BT, Price J et al Detection of Brain Tau Pathology in Down Syndrome Using Plasma Biomarkers. JAMA Neurol. Published online July 5, 2022 PMID: 35789365 https://jamanetwork.com/journals/jamaneurology/fullarticle/2793702
  11. Liang F, Baldyga K, Quan Q et al Preoperative Plasma Tau-PT217 and Tau-PT181 Are Associated With Postoperative Delirium Annals of Surgery. 2022 July 6 PMID: 35794069 https://journals.lww.com/annalsofsurgery/Abstract/9900/Preoperative_Plasma_Tau_PT217_and_Tau_PT181_Are.70.aspx
  12. Morrison MS et al. Antemortem plasma phosphorylated tau (181) predicts Alzheimer's disease neuropathology and regional tau at autopsy. Brain 2022 May 13; [e-pub] PMID: 35554506 https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awac175/6585495
  13. George J Blood Test Predicts Which People With Amyloid Are Likely to Decline Cognitively. Plasma p-tau217 outperformed other preclinical Alzheimer's measures. MedPage Today February 6, 2023 https://www.medpagetoday.com/neurology/alzheimersdisease/102970 - Mattsson-Carlgren N, Salvado G, Ashton NJ et al Prediction of Longitudinal Cognitive Decline in Preclinical Alzheimer Disease Using Plasma Biomarkers. JAMA Neurol. Published online February 6, 2023 PMID: 36745413 https://jamanetwork.com/journals/jamaneurology/fullarticle/2801289
  14. Dark HE, Paterson C, Daya GN et al Proteomic Indicators of Health Predict Alzheimer's Disease Biomarker Levels and Dementia Risk. Ann Neurol. 2023. Oct 6. PMID: 37801487 https://onlinelibrary.wiley.com/doi/full/10.1002/ana.26817
  15. George J Alzheimer's Blood Test Predicts Who Might Benefit Most From Anti-Amyloid Drugs. Novel two-cutoff approach may reduce need for confirmatory PET scans. MedPage Today December 5, 2023 https://www.medpagetoday.com/neurology/alzheimersdisease/107691 - Mattsson-Carlgren N, Collij LE, Stomrud E et al Plasma Biomarker Strategy for Selecting Patients With Alzheimer Disease for Antiamyloid Immunotherapies. JAMA Neurol. Published online December 4, 2023. PMID: 38048096 https://jamanetwork.com/journals/jamaneurology/article-abstract/2812432
  16. Mielke MM, Dage JL, Frank RD et al Performance of plasma phosphorylated tau 181 and 217 in the community. Nat Med. 2022 Jul;28(7):1398-1405. PMID: 35618838 PMCID: PMC9329262 Free PMC article.
  17. Thermo Fischer Scientific Antibody Protocol Collection https://www.thermofisher.com/us/en/home/life-science/antibodies/antibodies-learning-center/antibody-protocols.html
  18. Ashton NJ, Brum WS, Di Molfetta G et al Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology. JAMA Neurol. Published online January 22, 2024 PMID: 38252443 https://jamanetwork.com/journals/jamaneurology/fullarticle/2813751

Component-of

PrecivityAD2 blood test algorithm; amyloid probability score 2 (APS2); plasma ptau217/total tau + amyloid-beta-42/amyloid-beta-40 in plasma