Brain : a journal of neurologyJan 29, 2025

Blood levels of a specific tau protein linked to memory problems in Alzheimer's disease

Alzheimers & Treatments Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 4, 2026

Abstract

Plasma p-tau217 is more strongly associated with cognitive performance than p-tau181 and p-tau231.

Plasma p-tau217 shows a particularly strong relationship with memory scores in both the TRIAD and BioFINDER-2 cohorts.
In cognitively impaired individuals, associations between plasma p-tau biomarkers and cognitive scores are pronounced.
Plasma p-tau217 outperforms p-tau181 and p-tau231 in identifying memory impairment, as indicated by area under the curve values of 0.86 for both cohorts.
Cognitive deficits were observed in amyloid-β-positive individuals, even in those with low plasma tau levels, indicating the presence of subtle memory deficits.
Significant cognitive deficits were found across all biomarkers in participants without significant tau in the neocortex.

Simplified

(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.

Key numbers

-0.53

Memory Score Association (β)

Regression coefficient for plasma p-tau217 in the TRIAD cohort.

0.86

Memory Impairment Detection AUC

Area under the curve for plasma p-tau217 in both cohorts.

P < 0.001

Cognitive Deficits in A+T1+T2-

Statistical significance for cognitive deficits observed in both cohorts.

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Funding

Competing interests

G.S. has received speaker fees from Springer and Adium. G.T.-B. receives salary and stock from Johnson & Johnson. He also holds patents for Janssen Simoa assays CSF p217+Tau, Plasma p217+Tau, and plasma CD tTau assays, respectively. S.P. has acquired research support (for the institution) from Avid and ki elements through ADDF. In the past 2 years, he has received consultancy/speaker fees from BioArtic, Biogen, Eisai, Eli Lilly, Novo Nordisk, and Roche. H.Z. has served at scientific advisory boards and/or as a consultant for AbbVie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, NervGen, Novo Nordisk, OptoCeutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; has given lectures in symposia sponsored by AlzeCure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). K.B. has served as a consultant and at advisory boards for AbbVie, AC Immune, ALZpath, AriBio, Beckman Coulter, BioArctic, Biogen, Eisai, Lilly, Moleac Pte Ltd, Neurimmune, Novartis, Ono Pharma, Prothena, Quanterix, Roche Diagnostics, Sanofi and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials, and participated in educational programmes for AC Immune, Biogen, Celdara Medical, Eisai, and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. O.H. is an employee of Eli Lilly and Lund University. The other authors have no competing interests to disclose.

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Blood levels of a specific tau protein linked to memory problems in Alzheimer's disease

Abstract

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