Toni T Saari, Teemu Palviainen, Mikko Hiltunen, Sanna-Kaisa Herukka, Tarja Kokkola, Sari Kärkkäinen, Mia Urjansson, Aino Aaltonen, Aarno Palotie, Heiko Runz, Jaakko Kaprio, Valtteri Julkunen, Eero Vuoksimaa
{"title":"无痴呆患者血浆磷酸化tau 217的横断面研究。","authors":"Toni T Saari, Teemu Palviainen, Mikko Hiltunen, Sanna-Kaisa Herukka, Tarja Kokkola, Sari Kärkkäinen, Mia Urjansson, Aino Aaltonen, Aarno Palotie, Heiko Runz, Jaakko Kaprio, Valtteri Julkunen, Eero Vuoksimaa","doi":"10.1002/dad2.70107","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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).</p><p><strong>Methods: </strong>A population-based biobank recall study of 65- to 85-year-old twins (<i>N</i> = 697, mean [SD] age 76.2 [4.6] years; 53% women, 154 full pairs) excluding those with AD based on health registry data.</p><p><strong>Results: </strong>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 (<i>APOE</i>) ε4 allele. Heritability was 0.56 (95% confidence interval [CI]: 0.36-0.79) and GWAS indicated 45 single nucleotide polymorphisms (SNPs) (<i>p </i>< 5 × 10<sup>-08</sup>) centered around the <i>APOE</i> locus.</p><p><strong>Discussion: </strong>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.</p><p><strong>Highlights: </strong>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 (<i>APOE</i>) 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 <i>APOE</i> region.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 2","pages":"e70107"},"PeriodicalIF":4.0000,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064337/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cross-sectional study of plasma phosphorylated tau 217 in persons without dementia.\",\"authors\":\"Toni T Saari, Teemu Palviainen, Mikko Hiltunen, Sanna-Kaisa Herukka, Tarja Kokkola, Sari Kärkkäinen, Mia Urjansson, Aino Aaltonen, Aarno Palotie, Heiko Runz, Jaakko Kaprio, Valtteri Julkunen, Eero Vuoksimaa\",\"doi\":\"10.1002/dad2.70107\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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).</p><p><strong>Methods: </strong>A population-based biobank recall study of 65- to 85-year-old twins (<i>N</i> = 697, mean [SD] age 76.2 [4.6] years; 53% women, 154 full pairs) excluding those with AD based on health registry data.</p><p><strong>Results: </strong>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 (<i>APOE</i>) ε4 allele. Heritability was 0.56 (95% confidence interval [CI]: 0.36-0.79) and GWAS indicated 45 single nucleotide polymorphisms (SNPs) (<i>p </i>< 5 × 10<sup>-08</sup>) centered around the <i>APOE</i> locus.</p><p><strong>Discussion: </strong>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.</p><p><strong>Highlights: </strong>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 (<i>APOE</i>) 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 <i>APOE</i> region.</p>\",\"PeriodicalId\":53226,\"journal\":{\"name\":\"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring\",\"volume\":\"17 2\",\"pages\":\"e70107\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-05-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064337/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/dad2.70107\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/dad2.70107","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Cross-sectional study of plasma phosphorylated tau 217 in persons without dementia.
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.
期刊介绍：
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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