Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer’s disease spectrum

Plasma phosphorylated tau (p-tau) biomarkers open unprecedented opportunities for identifying carriers of Alzheimer's disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment. To address this question, we included 103 cognitively unimpaired elderly and 40 cognitively impaired, amyloid-β-positive individuals from the TRIAD cohort, in addition to 336 cognitively unimpaired and 216 cognitively impaired, amyloid-β-positive older adults from the BioFINDER-2 cohort. Participants had tau PET scans, amyloid PET scans or amyloid CSF, p-tau217, p-tau181 and p-tau231 blood measures, structural T1-MRI and cognitive assessments. In this cross-sectional study, we used regression models and correlation analyses to assess the relationship between plasma biomarkers and cognitive scores. Furthermore, we applied receiver operating characteristic curves to assess cognitive impairment across plasma biomarkers. Finally, we categorized participants into amyloid (A), p-tau (T1) and tau PET (T2) positive (+) or negative (-) profiles and ran non-parametric comparisons to assess differences across cognitive domains. We found that plasma p-tau217 was more associated with cognitive performance than p-tau181 and p-tau231 and that this relationship was particularly strong for memory scores (TRIAD: βp-tau217 = -0.53, βp-tau181 = -0.35 and βp-tau231 = -0.24; BioFINDER-2: βp-tau217 = -0.52, βp-tau181 = -0.24 and βp-tau231 = -0.29). Associations in amyloid-β-positive participants resembled these results, but other cognitive scores also showed strong associations in cognitively impaired individuals. Moreover, plasma p-tau217 outperformed plasma p-tau181 and plasma p-tau231 in identifying memory impairment (area under the curve values for TRIAD: p-tau217 = 0.86, p-tau181 = 0.77 and p-tau231 = 0.75; and for BioFINDER-2: p-tau217 = 0.86, p-tau181 = 0.76 and p-tau231 = 0.81) and in identifying executive function impairment only in the BioFINDER-2 cohort (p-tau217 = 0.82, p-tau181 = 0.76 and p-tau231 = 0.76). Lastly, we showed that subtle memory deficits were present in A+T1+T2- participants for plasma p-tau217 (P = 0.007) and plasma p-tau181 (P = 0.01) in the TRIAD cohort and for all biomarkers across cognitive domains in A+T1+T2- and A+T1+T2- individuals (P < 0.001 in all) in the BioFINDER-2 cohort. The A+T1+T2- individuals showed cognitive deficits in both cohorts (P < 0.001 in all). Together, our results suggest that plasma p-tau217 stands out as a biomarker capable of identifying memory deficits attributable to Alzheimer's disease and that memory impairment certainly occurs in amyloid-β- and plasma p-tau-positive individuals who have no significant amounts of tau in the neocortex.

Authors

Institutions

Publication Details

Journal
Brain
Published
2025-01-29
DOI
https://doi.org/10.1093/brain/awaf033
Citations
14
Primary Topic
Alzheimer's disease research and treatments
Type
article
Field-Weighted Citation Impact
16.30
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer’s disease spectrum

Yasser Iturria‐Medina, Tharick Ali Pascoal, Joseph Therriault, Nicholas James Ashton et al.
14 citations
Brain
Alzheimer's disease research and treatments
16.30
article

Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer’s disease spectrum

Yasser Iturria‐Medina, Tharick Ali Pascoal, Joseph Therriault, Nicholas James Ashton, Paolo Vitali, Eduardo Rigon Zimmer, Swagatika Mohapatra, Sebastian Palmqvist, Erik Stomrud, Wan Lu Jia, Wagner S. Brum, Jesse Klostranec, Jaime Fernández Arias, Sulantha Mathotaarachchi, Niklas Mattsson, Nesrine Rahmouni, Andréa Lessa Benedet, Oskar Hansson, Arthur C. Macedo, Thomas K. Karikari, Peter Kunach, Tevy Chan, Brandon J. Hall, Seyyed Ali Hosseini, Gemma Salvadó, Stijn Servaes, Yi‐Ting Wang, Gallen Triana‐Baltzer, Maxime Montembeault, Hartmuth C. Kolb, Cécile Tissot, Kely Quispialaya, Kaj Blennow, Henrik Zetterberg, Étienne Aumont, Gleb Bezgin, Pedro Rosa‐Neto, Yingying Zheng, Shorena Janelidze, Lydia Trudel
article en
14 citations

Abstract

Plasma phosphorylated tau (p-tau) biomarkers open unprecedented opportunities for identifying carriers of Alzheimer's disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment. To address this question, we included 103 cognitively unimpaired elderly and 40 cognitively impaired, amyloid-β-positive individuals from the TRIAD cohort, in addition to 336 cognitively unimpaired and 216 cognitively impaired, amyloid-β-positive older adults from the BioFINDER-2 cohort. Participants had tau PET scans, amyloid PET scans or amyloid CSF, p-tau217, p-tau181 and p-tau231 blood measures, structural T1-MRI and cognitive assessments. In this cross-sectional study, we used regression models and correlation analyses to assess the relationship between plasma biomarkers and cognitive scores. Furthermore, we applied receiver operating characteristic curves to assess cognitive impairment across plasma biomarkers. Finally, we categorized participants into amyloid (A), p-tau (T1) and tau PET (T2) positive (+) or negative (-) profiles and ran non-parametric comparisons to assess differences across cognitive domains. We found that plasma p-tau217 was more associated with cognitive performance than p-tau181 and p-tau231 and that this relationship was particularly strong for memory scores (TRIAD: βp-tau217 = -0.53, βp-tau181 = -0.35 and βp-tau231 = -0.24; BioFINDER-2: βp-tau217 = -0.52, βp-tau181 = -0.24 and βp-tau231 = -0.29). Associations in amyloid-β-positive participants resembled these results, but other cognitive scores also showed strong associations in cognitively impaired individuals. Moreover, plasma p-tau217 outperformed plasma p-tau181 and plasma p-tau231 in identifying memory impairment (area under the curve values for TRIAD: p-tau217 = 0.86, p-tau181 = 0.77 and p-tau231 = 0.75; and for BioFINDER-2: p-tau217 = 0.86, p-tau181 = 0.76 and p-tau231 = 0.81) and in identifying executive function impairment only in the BioFINDER-2 cohort (p-tau217 = 0.82, p-tau181 = 0.76 and p-tau231 = 0.76). Lastly, we showed that subtle memory deficits were present in A+T1+T2- participants for plasma p-tau217 (P = 0.007) and plasma p-tau181 (P = 0.01) in the TRIAD cohort and for all biomarkers across cognitive domains in A+T1+T2- and A+T1+T2- individuals (P < 0.001 in all) in the BioFINDER-2 cohort. The A+T1+T2- individuals showed cognitive deficits in both cohorts (P < 0.001 in all). Together, our results suggest that plasma p-tau217 stands out as a biomarker capable of identifying memory deficits attributable to Alzheimer's disease and that memory impairment certainly occurs in amyloid-β- and plasma p-tau-positive individuals who have no significant amounts of tau in the neocortex.

BrainVol. 148(7)
University of Science and Technology of China (CN), Montreal Neurological Institute and Hospital (CA), Universidade Federal do Rio Grande do Sul (BR), University of Wisconsin–Madison (US), Janssen (Belgium) (BE), Lawrence Berkeley National Laboratory (US), Université du Québec à Montréal (CA), University of Pittsburgh (US), Lund University (SE), Douglas Mental Health University Institute (CA), Hong Kong Science and Technology Parks Corporation (HK), Sahlgrenska University Hospital (SE), McGill University Health Centre (CA), Banner Health (US), Sorbonne Université (FR), Pitié-Salpêtrière Hospital (FR), UK Dementia Research Institute (GB), MRC Prion Unit (GB), Skåne University Hospital (SE), Banner Sun Health Research Institute (US), Janssen (United States) (US), National Hospital for Neurology and Neurosurgery (GB), Institut du Cerveau (FR), The Memory Clinic (US), University College London (GB), McGill University (CA), The University of Texas Southwestern Medical Center (US), University of Gothenburg (SE)
Openalex Percentile: Top 1%
Alzheimer's disease research and treatments
16.30
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.