Saari Toni T, Palviainen Teemu, Hiltunen Mikko, Herukka Sanna-Kaisa, Kokkola Tarja, Kärkkäinen Sari, Urjansson Mia, Aaltonen Aino, Palotie Aarno, Runz Heiko, Kaprio Jaakko, Julkunen Valtteri, Vuoksimaa Eero
Institute for Molecular Medicine Finland (FIMM) Helsinki Institute of Life Science University of Helsinki Helsinki Finland.
Institute of Biomedicine University of Eastern Finland Kuopio Finland.
Alzheimers Dement (Amst). 2025 May 9;17(2):e70107. doi: 10.1002/dad2.70107. eCollection 2025 Apr-Jun.
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).
A population-based biobank recall study of 65- to 85-year-old twins ( = 697, mean [SD] age 76.2 [4.6] years; 53% women, 154 full pairs) excluding those with AD based on health registry data.
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 () ε4 allele. Heritability was 0.56 (95% confidence interval [CI]: 0.36-0.79) and GWAS indicated 45 single nucleotide polymorphisms (SNPs) (< 5 × 10) centered around the locus.
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.
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 () 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 region.
对于未临床诊断为阿尔茨海默病（AD）的个体，血浆磷酸化tau 217（p-tau217）的了解甚少。我们研究了血浆p-tau217与年龄、性别、教育程度和遗传风险的关联；估计了遗传力；并进行了全基因组关联研究（GWAS）。
一项基于人群的生物样本库回顾性研究，研究对象为65至85岁的双胞胎（n = 697，平均[标准差]年龄76.2[4.6]岁；53%为女性，154对同卵双胞胎），根据健康登记数据排除患有AD的个体。
较高的p-tau217水平和AD神经病理改变的可能性（p-tau217>0.42 pg/mL；39%有明显改变）与较高年龄和携带载脂蛋白E（ApoE）ε4等位基因有关。遗传力为0.56（95%置信区间[CI]：0.36 - 0.79），GWAS显示45个单核苷酸多态性（SNP）（P<5×10⁻⁸）集中在ApoE基因座周围。
我们的结果阐明了基于人群的p-tau217的特征和遗传关联。我们发现许多未临床诊断为AD的65至85岁个体基于血浆p-tau217存在AD神经病理改变。
血浆磷酸化tau 217（p-tau217）是阿尔茨海默病（AD）的一个有前景的生物标志物。我们在一个基于人群的65至85岁样本中研究了血浆p-tau217。我们排除了临床诊断为AD的个体。较高年龄和携带载脂蛋白E（ApoE）ε4等位基因与较高的血浆p-tau217有关。p-tau217的遗传力为56%，全基因组关联研究（GWAS）表明ApoE区域周围的基因与之相关。
