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

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

  • By

  • Jaime Fernández Arias

  • Wagner S Brum

  • Gemma Salvadó

  • Joseph Therriault

  • Stijn Servaes

  • Yi-Ting Wang

  • Etienne Aumont

  • Nesrine Rahmouni

  • Arthur C Macedo

  • Kely Monica Quispialaya

  • Seyyed Ali Hosseini

  • Peter Kunach

  • Wan Lu Jia

  • Tevy Chan

  • Lydia Trudel

  • Brandon Hall

  • Yanseng Zheng

  • Sejal Mohapatra

  • Sulantha S Mathotaarachchi

  • Paolo Vitali

  • Cécile Tissot

  • Gleb Bezgin

  • Yasser Iturria-Medina

  • Nicholas J Ashton

  • Andréa Lessa Benedet

  • Thomas K Karikari

  • Gallen Triana-Baltzer

  • Jesse M Klostranec

  • Hartmuth C Kolb

  • Eduardo R Zimmer

  • Shorena Janelidze

  • Niklas Mattsson-Carlgren

  • Erik Stomrud

  • Sebastian Palmqvist

  • Henrik Zetterberg

  • Kaj Blennow

  • Tharick Pascoal

  • Maxime Montembeault

  • Oskar Hansson

  • Pedro Rosa-Neto

  • January 29, 2025

  • 0 min

Share

Elevated Plasma p-tau217 Correlates with Cognitive Impairments in Alzheimer’s Disease

Overview

This study demonstrates that plasma phosphorylated tau217 (p-tau217) levels are more strongly associated with cognitive impairments, especially memory deficits, in Alzheimer’s disease (AD) than p-tau181 and p-tau231. Plasma p-tau217 also better identifies cognitive impairment across cohorts and reveals subtle memory deficits in amyloid-β- and plasma p-tau-positive individuals without significant neocortical tau deposition.

Background

Alzheimer’s disease is characterized by amyloid-β plaques and tau neurofibrillary tangles, with tau pathology closely linked to cognitive decline. Plasma phosphorylated tau biomarkers reflect tau phosphorylation and secretion and offer minimally invasive detection of AD pathophysiology. Cognitive deficits in AD typically begin with memory impairment, and recent frameworks distinguish fluid p-tau biomarkers (T1) from tau PET biomarkers (T2) to better stage disease progression. Understanding how plasma p-tau biomarkers relate to cognitive domains can improve early detection and staging of AD.

Data Highlights

BiomarkerMemory Association (β)Memory Impairment AUC (TRIAD)Memory Impairment AUC (BioFINDER-2)Executive Function Impairment AUC (BioFINDER-2)
p-tau217TRIAD: -0.53
BioFINDER-2: -0.52		0.860.860.82
p-tau181TRIAD: -0.35
BioFINDER-2: -0.24		0.770.760.76
p-tau231TRIAD: -0.24
BioFINDER-2: -0.29		0.750.810.76

Key Findings

  • Plasma p-tau217 shows stronger associations with cognitive performance, particularly memory, than p-tau181 and p-tau231 in both TRIAD and BioFINDER-2 cohorts.
  • Plasma p-tau217 outperforms other plasma p-tau biomarkers in identifying memory impairment, with AUC values of 0.86 in both cohorts.
  • In the BioFINDER-2 cohort, plasma p-tau217 also better identifies executive function impairment compared to p-tau181 and p-tau231.
  • Subtle memory deficits are detectable in amyloid-β-positive, plasma p-tau-positive but tau PET-negative (A+T1+T2−) individuals, indicating early cognitive changes before neocortical tau accumulation.
  • The ATN biomarker framework incorporating plasma p-tau biomarkers (T1) and tau PET (T2) helps clarify cognitive deficits across AD stages.

Clinical Implications

Plasma p-tau217 is a promising minimally invasive biomarker for early detection of memory impairment in Alzheimer’s disease, potentially enabling earlier diagnosis and intervention. Its superior performance over other plasma p-tau isoforms supports its use in clinical settings to monitor cognitive decline and stratify patients according to disease stage, even before significant tau PET positivity. Incorporating plasma p-tau217 into the ATN framework may improve staging and management of AD.

Conclusion

Plasma p-tau217 is a robust biomarker that correlates strongly with memory deficits in Alzheimer’s disease and can identify cognitive impairment earlier than other plasma p-tau isoforms. These findings support its clinical utility in detecting and monitoring AD-related cognitive decline.

References

  1. Original Article 2024 -- Elevated Plasma Phosphorylated Tau217 Correlates with Cognitive Impairments in the Spectrum of Alzheimer’s Disease

Original Source(s)

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

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

  • January 29, 2025

Related Content

Open Your Eyes and Eliminate Bad Stress, Starting Now

Drawing on Blue Zones research, Dr. Jasper lists tips to manage stress and overall health.

Editorial: Transforming dementia caregiving through assistive technologies

Advancing Alzheimer Disease Prediction With Large Language Model–Based Linguistic Feature Analysis: Development and Validation Study