Plasma p-tau217 in Alzheimer's disease: Lumipulse and ALZpath SIMOA head-to-head comparison

Abstract

Plasma phosphorylated-tau217 (p-tau217) has been shown to be one of the most accurate diagnostic markers for Alzheimer's disease. No studies have compared the clinical performance of p-tau217 as assessed by the fully automated Lumipulse and single molecule array (SIMOA) AlZpath p-tau217. The study included 392 participants, 162 with Alzheimer's disease, 70 with other neurodegenerative diseases with CSF biomarkers and 160 healthy controls. Plasma p-tau217 levels were measured using the Lumipulse and ALZpath SIMOA assays. The ability of p-tau217 assessed by both techniques to discriminate Alzheimer's disease from other neurodegenerative diseases and controls was investigated using receiver operating characteristic analyses. The p-tau217 levels measured by the two techniques demonstrated a strong correlation, showing a consistent relationship with CSF p-tau181 levels. In head-to-head comparison, Lumipulse and SIMOA showed similar diagnostic accuracy for differentiating Alzheimer's disease from other neurodegenerative diseases [area under the curve (AUC) 0.952, 95% confidence interval (CI) 0.927-0.978 versus 0.955, 95% CI 0.928-0.982, respectively] and healthy controls (AUC 0.938, 95% CI 0.910-0.966 and 0.937, 95% CI 0.907-0.967 for both assays). This study demonstrated the high precision and diagnostic accuracy of p-tau217 for the clinical diagnosis of Alzheimer's disease using fully automated or semi-automated techniques.

The research is supported by an Associazione Italiana Ricerca Alzheimer AGYR2021 Life-Bio Grant, Ministero dell’Istruzione, dell’Università e della Ricerca, Italy, PRIN COCOON (2017MYJ5TH) and PRIN 2021 RePlast (2020PNRR2THZAW), Ministero della Salute, Italy, Grant/Award Number: RF-2018-12366209 and PNRR-Health PNRR-MAD-2022-12376110. A.Pi. has been supported by grants from the Associazione Italiana Ricerca Alzheimer AGYR2021 Life-Bio Grant, the LIMPE-DISMOV Foundation Segala Grant 2021, Ministero dell’Istruzione, dell’Università e della Ricerca PRIN COCOON (2017MYJ5TH) and PRIN 2021 RePlast (20202THZAW), the H2020 European Research Council IMI IDEA-FAST (ID853981), Ministero della Salute Grant/Award Number: RF-2018-12366209 and PNRR-Health PNRR-MAD-2022-12376110. V.Q. is supported by the H2020 IMI IDEA-FAST (ID853981). C.Tra. is supported by Ministero dell’Istruzione, dell’Università e della Ricerca. C.To. is supported by the Ministero della Salute PRIN 2021 RePlast. A.G. is supported by the Ministero della Salute PRIN 2021 RePlast and the H2020 European Research Council IMI IDEA-FAST (ID853981). A.R. is supported by the H2020 European Research Council IMI IDEA-FAST (ID853981) and the PNRR-Health PNRR-MAD-2022-12376110. O.H. was supported by the European Research Council (ADG-101096455), Alzheimer’s Association (ZEN24-1069572, SG-23-1061717), the GHR Foundation, Vetenskapsrådet (2022-00775), ERA PerMed (ERAPERMED2021-184), Knut och Alice Wallenberg Stiftelse (2022-0231), Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University, Alzheimerfonden (AF-980907), Hjärnfonden (FO2021-0293), Parkinsonfonden (1412/22), the Cure Alzheimer’s Fund, Rönström Family Foundation, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Skåne University Hospital Foundation (2020-O000028), Region Skåne Regionalt Forskningsstöd (2022-1259) and the Swedish federal government under the ALF agreement (2022-Projekt0080). S.P. is supported by the National Institute on Aging (USA; #R01AG083740), the Swedish Research Council (#2018-02052), Alzheimerfonden (#AF-994075), Hjärnfonden (#FO2022-0204), and the Family Rönström’s Foundation (#FRS-0004). H.Z. is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council, supported by grants from the Swedish Research Council (#2023-00356; #2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation program under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer’s Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C, and #ADSF-24-1284328-C), the Bluefield Project, Cure Alzheimer’s Fund, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions grant agreement No 860197 (MIRIADE), the European Union Joint Programme—Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research UCLH Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003). K.B. is supported by the Swedish Research Council (2017-00915 and 2022-00732), Alzheimerfonden, Sweden (AF-930351, AF-939721, and AF-968270), Hjärnfonden, Sweden (FO2017-0243 and ALZ2022-0006), Swedish state under the agreement between the Swedish government and the County Councils, ALF-agreement (ALFGBG-715986 and ALFGBG-965240), European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495), and Alzheimer’s Association 2022-2025 grant (SG-23-1038904 QC). The Wisconsin Registry for Alzheimer’s Prevention is supported by National Institutes of Health grants AG027161 and AG021155. M.S.C. receives funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 948677); ERA PerMed (ERAPERMED2021-184); Project ‘PI19/00155’ and ‘PI22/00456, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union; and from a fellowship from ‘la Caixa’ Foundation (ID 100010434) and from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions grant agreement No 847648 (LCF/BQ/PR21/11840004). A.Pa. has been supported by grants of the Ministero dell’Istruzione, dell’Università e della Ricerca PRIN COCOON (2017MYJ5TH) and PRIN 2021 RePlast (20202THZAW), the H2020 IMI IDEA-FAST (ID853981), Italian Ministry of Health, Grant/Award Number: RF-2018-12366209, RF-2019-12369272 and PNRR-Health PNRR-MAD-2022-12376110.