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Comparison of plasma ALZpath p-Tau217 with Lilly p-Tau217 and p-Tau181 in a neuropathological cohort

Bali, Divya LU ; Salvadó, Gemma LU ; Beach, Thomas G. ; Serrano, Geidy E. ; Atri, Alireza ; Reiman, Eric M. ; Jeromin, Andreas ; Hansson, Oskar LU orcid and Janelidze, Shorena LU (2025) In Acta Neuropathologica Communications 13(1).
Abstract

There is an urgent need for accurate and validated methods to measure plasma phosphorylated tau (p-Tau) biomarkers in Alzheimer’s disease (AD). In this study, we compared the performance of new commercially available plasma p-Tau217 assay developed by ALZpath to other established p-Tau assays in an autopsy-confirmed sample. We included 72 participants from the Arizona Study of Aging and Neurodegenerative Disorders cohort, with antemortem plasma assessments and postmortem neuropathological examination. Plasma p-Tau217 was measured using the single molecule arrays (SIMOA)-based ALZpath immunoassay and plasma p-Tau217 and p-Tau181 were analyzed with mesoscale discovery (MSD)-based immunoassays developed by Lilly Research Laboratories.... (More)

There is an urgent need for accurate and validated methods to measure plasma phosphorylated tau (p-Tau) biomarkers in Alzheimer’s disease (AD). In this study, we compared the performance of new commercially available plasma p-Tau217 assay developed by ALZpath to other established p-Tau assays in an autopsy-confirmed sample. We included 72 participants from the Arizona Study of Aging and Neurodegenerative Disorders cohort, with antemortem plasma assessments and postmortem neuropathological examination. Plasma p-Tau217 was measured using the single molecule arrays (SIMOA)-based ALZpath immunoassay and plasma p-Tau217 and p-Tau181 were analyzed with mesoscale discovery (MSD)-based immunoassays developed by Lilly Research Laboratories. Plasma biomarkers were compared with densities of post-mortem-assessed amyloid plaques and neurofibrillary changes. Levels of p-Tau217ALZpath, p-Tau217Lilly and p-Tau181Lilly were significantly associated with plaque (partial Spearman ρ = 0.58, ρ = 0.78, ρ = 0.65; p < 0.001) and neurofibrillary (ρ = 0.26, ρ = 0.51, ρ = 0.37; p < 0.05) density scores, adjusting for age, sex, and time of interval between blood sampling and death. All three biomarkers were also significantly associated with plaque density scores (p-Tau217ALZpath, ρ = 0.53; p-Tau217Lilly, ρ = 0.73; p-Tau181Lilly, ρ = 0.59; p < 0.001), when additionally adjusting for neurofibrillary density scores. However, only p-Tau217Lilly was significantly associated with neurofibrillary density scores (ρ = 0.32, p = 0.022), when adjusting for plaque density scores. The correlations of p-Tau217ALZpath and p-Tau181Lilly with plaque density scores were comparable, whereas p-Tau217Lilly exhibited significantly higher correlations with plaques (pdiff≤0.015) and neurofibrillary changes (pdiff≤0.004) than p-Tau217ALZpath. While p-Tau217ALZpath and p-Tau181Lilly predicted the presence of Alzheimer’s disease neuropathological change (ADNC), Braak staging (Braak 0-IV vs. Braak V-VI) and CERAD neuritic plaque classification (low/sparse vs. moderate/frequent) with similar accuracies (area under the curve [AUC]range, 0.74–0.79), p-Tau217Lilly AUCs were significantly higher (AUCrange,0.82–0.89, pdiff≤0.024) than the AUCs of p-Tau217ALZpath. In conclusion, p-Tau217ALZpath exhibited similar performance as p-Tau181Lilly but its correlations with core measures of AD pathology were significantly lower in comparison with p-Tau217Lilly. Future studies are warranted to replicate these findings in larger independent cohorts.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Amyloid plaques, Neurofibrillary changes, Phosphorylated-tau
in
Acta Neuropathologica Communications
volume
13
issue
1
article number
144
publisher
BioMed Central (BMC)
external identifiers
  • pmid:40588775
  • scopus:105009541938
ISSN
2051-5960
DOI
10.1186/s40478-025-02064-2
language
English
LU publication?
yes
id
b45be7fb-b377-4f22-80e1-6421b2231e3c
date added to LUP
2025-10-29 09:09:02
date last changed
2025-10-29 09:09:02
@article{b45be7fb-b377-4f22-80e1-6421b2231e3c,
  abstract     = {{<p>There is an urgent need for accurate and validated methods to measure plasma phosphorylated tau (p-Tau) biomarkers in Alzheimer’s disease (AD). In this study, we compared the performance of new commercially available plasma p-Tau217 assay developed by ALZpath to other established p-Tau assays in an autopsy-confirmed sample. We included 72 participants from the Arizona Study of Aging and Neurodegenerative Disorders cohort, with antemortem plasma assessments and postmortem neuropathological examination. Plasma p-Tau217 was measured using the single molecule arrays (SIMOA)-based ALZpath immunoassay and plasma p-Tau217 and p-Tau181 were analyzed with mesoscale discovery (MSD)-based immunoassays developed by Lilly Research Laboratories. Plasma biomarkers were compared with densities of post-mortem-assessed amyloid plaques and neurofibrillary changes. Levels of p-Tau217<sub>ALZpath</sub>, p-Tau217<sub>Lilly</sub> and p-Tau181<sub>Lilly</sub> were significantly associated with plaque (partial Spearman ρ = 0.58, ρ = 0.78, ρ = 0.65; p &lt; 0.001) and neurofibrillary (ρ = 0.26, ρ = 0.51, ρ = 0.37; p &lt; 0.05) density scores, adjusting for age, sex, and time of interval between blood sampling and death. All three biomarkers were also significantly associated with plaque density scores (p-Tau217<sub>ALZpath</sub>, ρ = 0.53; p-Tau217<sub>Lilly</sub>, ρ = 0.73; p-Tau181<sub>Lilly</sub>, ρ = 0.59; p &lt; 0.001), when additionally adjusting for neurofibrillary density scores. However, only p-Tau217<sub>Lilly</sub> was significantly associated with neurofibrillary density scores (ρ = 0.32, p = 0.022), when adjusting for plaque density scores. The correlations of p-Tau217<sub>ALZpath</sub> and p-Tau181<sub>Lilly</sub> with plaque density scores were comparable, whereas p-Tau217<sub>Lilly</sub> exhibited significantly higher correlations with plaques (p<sub>diff</sub>≤0.015) and neurofibrillary changes (p<sub>diff</sub>≤0.004) than p-Tau217<sub>ALZpath</sub>. While p-Tau217<sub>ALZpath</sub> and p-Tau181<sub>Lilly</sub> predicted the presence of Alzheimer’s disease neuropathological change (ADNC), Braak staging (Braak 0-IV vs. Braak V-VI) and CERAD neuritic plaque classification (low/sparse vs. moderate/frequent) with similar accuracies (area under the curve [AUC]<sub>range</sub>, 0.74–0.79), p-Tau217<sub>Lilly</sub> AUCs were significantly higher (AUC<sub>range</sub>,0.82–0.89, p<sub>diff</sub>≤0.024) than the AUCs of p-Tau217<sub>ALZpath</sub>. In conclusion, p-Tau217<sub>ALZpath</sub> exhibited similar performance as p-Tau181<sub>Lilly</sub> but its correlations with core measures of AD pathology were significantly lower in comparison with p-Tau217<sub>Lilly</sub>. Future studies are warranted to replicate these findings in larger independent cohorts.</p>}},
  author       = {{Bali, Divya and Salvadó, Gemma and Beach, Thomas G. and Serrano, Geidy E. and Atri, Alireza and Reiman, Eric M. and Jeromin, Andreas and Hansson, Oskar and Janelidze, Shorena}},
  issn         = {{2051-5960}},
  keywords     = {{Alzheimer’s disease; Amyloid plaques; Neurofibrillary changes; Phosphorylated-tau}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Acta Neuropathologica Communications}},
  title        = {{Comparison of plasma ALZpath p-Tau217 with Lilly p-Tau217 and p-Tau181 in a neuropathological cohort}},
  url          = {{http://dx.doi.org/10.1186/s40478-025-02064-2}},
  doi          = {{10.1186/s40478-025-02064-2}},
  volume       = {{13}},
  year         = {{2025}},
}