Genetic and environmental contributions to variation in plasma phosphorylated tau 217

Rebecca Z. Rousset; Conor V. Dolan; David H. Wilson; Lisanne in ‘t Veld; Lannie Ligthart; Charlotte E. Teunissen; Eco J.C. de Geus; Anouk den Braber

doi:10.1002/alz.70906

Genetic and environmental contributions to variation in plasma phosphorylated tau 217

Rebecca Z. Rousset^*, Conor V. Dolan, David H. Wilson, Lisanne in ‘t Veld, Lannie Ligthart, Charlotte E. Teunissen, Eco J.C. de Geus, Anouk den Braber

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

INTRODUCTION: Plasma phosphorylated tau 217 (p-au217) is a promising Alzheimer's disease (AD) biomarker. Little is known about the causes of variance in p-tau217 concentrations in cognitively unimpaired populations. METHODS: The present sample included cognitively healthy twins and their family members (n = 6495). Biometric twin models were used to determine relative genetic and environmental contributions to variance in p-tau217, and genetic and environmental correlations between p-tau217 and neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta 42/40 (Aβ42/40). RESULTS: Genetic contributions accounted for 42% (males) and 41% (females) of variance in p-tau217. Half of the genetic effects were sex specific. Genetic and environmental contributions to p-tau217 were partially shared with NfL, GFAP, and Aβ42/40, but different patterns were found in males and females. DISCUSSION: P-tau217 concentrations are moderately heritable. Sex-specific genetic influences are found to act on p-tau217. In cognitively unimpaired participants, p-tau217 and Aβ42/40 reflect different biological processes. Highlights: Phosphorylated tau (p-tau)217 concentrations are substantially heritable (> 41%). Genetic contributions to variation in plasma p-tau217 were found to be sex specific. Genetic and environmental correlations were found between p-tau217 and Alzheimer's disease biomarkers. P-tau217 reflects different processes in cognitively unimpaired males and females.

Original language	English
Article number	e70906
Journal	Alzheimer's and Dementia
Volume	21
Issue number	11
DOIs	https://doi.org/10.1002/alz.70906
Publication status	Published - 13 Nov 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Keywords

biometric twin model
cognitively healthy population
environmental factors
genetic factors
phosphorylated tau 217
plasma biomarkers
sex differences

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@article{b964dadc4ce242baa745f3d6f37767b8,

title = "Genetic and environmental contributions to variation in plasma phosphorylated tau 217",

abstract = "INTRODUCTION: Plasma phosphorylated tau 217 (p-au217) is a promising Alzheimer's disease (AD) biomarker. Little is known about the causes of variance in p-tau217 concentrations in cognitively unimpaired populations. METHODS: The present sample included cognitively healthy twins and their family members (n = 6495). Biometric twin models were used to determine relative genetic and environmental contributions to variance in p-tau217, and genetic and environmental correlations between p-tau217 and neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta 42/40 (Aβ42/40). RESULTS: Genetic contributions accounted for 42\% (males) and 41\% (females) of variance in p-tau217. Half of the genetic effects were sex specific. Genetic and environmental contributions to p-tau217 were partially shared with NfL, GFAP, and Aβ42/40, but different patterns were found in males and females. DISCUSSION: P-tau217 concentrations are moderately heritable. Sex-specific genetic influences are found to act on p-tau217. In cognitively unimpaired participants, p-tau217 and Aβ42/40 reflect different biological processes. Highlights: Phosphorylated tau (p-tau)217 concentrations are substantially heritable (> 41\%). Genetic contributions to variation in plasma p-tau217 were found to be sex specific. Genetic and environmental correlations were found between p-tau217 and Alzheimer's disease biomarkers. P-tau217 reflects different processes in cognitively unimpaired males and females.",

keywords = "biometric twin model, cognitively healthy population, environmental factors, genetic factors, phosphorylated tau 217, plasma biomarkers, sex differences",

author = "Rousset, \{Rebecca Z.\} and Dolan, \{Conor V.\} and Wilson, \{David H.\} and \{in {\textquoteleft}t Veld\}, Lisanne and Lannie Ligthart and Teunissen, \{Charlotte E.\} and \{de Geus\}, \{Eco J.C.\} and \{den Braber\}, Anouk",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2025",

month = nov,

day = "13",

doi = "10.1002/alz.70906",

language = "English",

volume = "21",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "John Wiley and Sons Inc.",

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T1 - Genetic and environmental contributions to variation in plasma phosphorylated tau 217

AU - Rousset, Rebecca Z.

AU - Dolan, Conor V.

AU - Wilson, David H.

AU - in ‘t Veld, Lisanne

AU - Ligthart, Lannie

AU - Teunissen, Charlotte E.

AU - de Geus, Eco J.C.

AU - den Braber, Anouk

PY - 2025/11/13

Y1 - 2025/11/13

N2 - INTRODUCTION: Plasma phosphorylated tau 217 (p-au217) is a promising Alzheimer's disease (AD) biomarker. Little is known about the causes of variance in p-tau217 concentrations in cognitively unimpaired populations. METHODS: The present sample included cognitively healthy twins and their family members (n = 6495). Biometric twin models were used to determine relative genetic and environmental contributions to variance in p-tau217, and genetic and environmental correlations between p-tau217 and neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta 42/40 (Aβ42/40). RESULTS: Genetic contributions accounted for 42% (males) and 41% (females) of variance in p-tau217. Half of the genetic effects were sex specific. Genetic and environmental contributions to p-tau217 were partially shared with NfL, GFAP, and Aβ42/40, but different patterns were found in males and females. DISCUSSION: P-tau217 concentrations are moderately heritable. Sex-specific genetic influences are found to act on p-tau217. In cognitively unimpaired participants, p-tau217 and Aβ42/40 reflect different biological processes. Highlights: Phosphorylated tau (p-tau)217 concentrations are substantially heritable (> 41%). Genetic contributions to variation in plasma p-tau217 were found to be sex specific. Genetic and environmental correlations were found between p-tau217 and Alzheimer's disease biomarkers. P-tau217 reflects different processes in cognitively unimpaired males and females.

AB - INTRODUCTION: Plasma phosphorylated tau 217 (p-au217) is a promising Alzheimer's disease (AD) biomarker. Little is known about the causes of variance in p-tau217 concentrations in cognitively unimpaired populations. METHODS: The present sample included cognitively healthy twins and their family members (n = 6495). Biometric twin models were used to determine relative genetic and environmental contributions to variance in p-tau217, and genetic and environmental correlations between p-tau217 and neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta 42/40 (Aβ42/40). RESULTS: Genetic contributions accounted for 42% (males) and 41% (females) of variance in p-tau217. Half of the genetic effects were sex specific. Genetic and environmental contributions to p-tau217 were partially shared with NfL, GFAP, and Aβ42/40, but different patterns were found in males and females. DISCUSSION: P-tau217 concentrations are moderately heritable. Sex-specific genetic influences are found to act on p-tau217. In cognitively unimpaired participants, p-tau217 and Aβ42/40 reflect different biological processes. Highlights: Phosphorylated tau (p-tau)217 concentrations are substantially heritable (> 41%). Genetic contributions to variation in plasma p-tau217 were found to be sex specific. Genetic and environmental correlations were found between p-tau217 and Alzheimer's disease biomarkers. P-tau217 reflects different processes in cognitively unimpaired males and females.

KW - biometric twin model

KW - cognitively healthy population

KW - environmental factors

KW - genetic factors

KW - phosphorylated tau 217

KW - plasma biomarkers

KW - sex differences

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DO - 10.1002/alz.70906

M3 - Article

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AN - SCOPUS:105021588692

SN - 1552-5260

VL - 21

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 11

M1 - e70906

ER -

Genetic and environmental contributions to variation in plasma phosphorylated tau 217

Abstract

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