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. 2025 May 9;17(2):e70107.
doi: 10.1002/dad2.70107. eCollection 2025 Apr-Jun.

Cross-sectional study of plasma phosphorylated tau 217 in persons without dementia

Toni T Saari  1 , Teemu Palviainen  1 , Mikko Hiltunen  2 , Sanna-Kaisa Herukka  3   4 , Tarja Kokkola  3 , Sari Kärkkäinen  3 , Mia Urjansson  1 , Aino Aaltonen  1 , Aarno Palotie  1   5   6 , Heiko Runz  1   7 , Jaakko Kaprio  1 , Valtteri Julkunen  1   3   4 , Eero Vuoksimaa  1 ; for FinnGen
Affiliations

Cross-sectional study of plasma phosphorylated tau 217 in persons without dementia

Toni T Saari et al. Alzheimers Dement (Amst). .

Abstract

Introduction: Little is known about plasma phosphorylated tau 217 (p-tau217) in individuals without a clinical diagnosis of Alzheimer's disease (AD). We studied associations of plasma p-tau217 with age, sex, education, and genetic risk; estimated the heritability; and conducted a genome-wide association study (GWAS).

Methods: A population-based biobank recall study of 65- to 85-year-old twins (N = 697, mean [SD] age 76.2 [4.6] years; 53% women, 154 full pairs) excluding those with AD based on health registry data.

Results: Higher p-tau217 level and likelihood of AD neuropathologic change (p-tau217 > 0.42 pg/mL; evident in 39%) were associated with higher age and having an apolipoprotein E (APOE) ε4 allele. Heritability was 0.56 (95% confidence interval [CI]: 0.36-0.79) and GWAS indicated 45 single nucleotide polymorphisms (SNPs) (p < 5 × 10-08) centered around the APOE locus.

Discussion: Our results elucidate the characteristics and genetic associations of p-tau217 in a population-based setting. We found many 65- to 85-year-olds without a clinical diagnosis of AD to have AD neuropathologic change based on plasma p-tau217.

Highlights: Plasma phosphorylated tau 217 (p-tau217) is a promising biomarker of Alzheimer's disease (AD).We studied plasma p-tau217 in a population-based sample of 65- to -85-year-olds.We excluded those with a clinical diagnosis of AD.Older age and having an apolipoprotein E (APOE) ε4 allele were associated with higher plasma p-tau217.Heritability of p-tau217 was 56% and a genome-wide association study (GWAS) implicated genes around the APOE region.

Keywords: Alzheimer's disease; apolipoprotein E; genome‐wide association study; plasma biomarkers; twins.

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Conflict of interest statement

A.P. is the Chief Scientific Officer of the FinnGen project, which is funded by 14 pharmaceutical companies. The FinnGen partner pharma companies are: AbbVie Inc., AstraZeneca UK Ltd, Biogen MA Inc., Bristol Myers Squibb (and Celgene Corporation & Celgene International II Sàrl), Genentech Inc., Merck Sharp & Dohme LCC, Pfizer Inc., GlaxoSmithKline Intellectual Property Development Ltd., Sanofi US Services Inc., Maze Therapeutics Inc., Janssen Biotech Inc, Novartis Pharma AG, Boehringer Ingelheim International GmbH, and Bayer. H.R. is a current employee of Insitro Inc., a former employee of Biogen, reports speaker's fees and travel payments from Roche and holds stock at Merck & Co and Biogen Inc. A.A. declares personal funding from the Finnish Cultural Foundation and Tauno Virtanen fund. E.V. reports Sigrid Jusélius Foundation and Research Council of Finland funding paid to the University of Helsinki. The authors declare no other competing financial or non‐financial interests. Author disclosures are available in the Supporting Information.

Figures

FIGURE 1
FIGURE 1
Phosphorylated tau 217 immunoassay levels in APOE ε4 carriers versus non‐carriers by age group (n = 695). APOE, apolipoprotein E.
FIGURE 2
FIGURE 2
Genome‐wide association analysis of p‐tau217. (A) Manhattan plot for the genome‐wide association analysis of p‐tau217. (B) Regional plot in the APOE locus in Chromosome 19 for the SNP associations with p‐tau217 with rs429358 as a reference. APOE, apolipoprotein E; p‐tau217, phosphorylated tau 217; SNP, single nucleotide polymorphism.
See this image and copyright information in PMC

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