Cross‐sectional study of plasma phosphorylated tau 217 in persons without dementia
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...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-04-01
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| Series: | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/dad2.70107 |
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| Summary: | 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. |
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| ISSN: | 2352-8729 |