%0 Journal Article
%A Mourtzi, Niki
%A Charisis, Sokratis
%A Ntanasi, Eva
%A Hatzimanolis, Alexandros
%A Ramirez, Alfredo
%A Sampatakakis, Stefanos N
%A Yannakoulia, Mary
%A Kosmidis, Mary H
%A Dardiotis, Efthimios
%A Hadjigeorgiou, George
%A Sakka, Paraskevi
%A Mamalaki, Eirini
%A Papandreou, Christopher
%A Georgakis, Marios K
%A Scarmeas, Nikolaos
%T Longitudinal Association of a Polygenic Risk Score for Plasma T-Tau With Incident Alzheimer Dementia and Mild Cognitive Impairment.
%J Neurology
%V 105
%N 9
%@ 0028-3878
%C Philadelphia, Pa.
%I Wolters Kluwer
%M DZNE-2025-01139
%P e213904
%D 2025
%X Elevated levels of total tau (t-tau) are a key biomarker of neurodegeneration, often seen in Alzheimer disease (AD). Identifying individuals at increased risk of AD using minimally invasive biomarkers can enable early intervention. We developed a polygenic risk score (PRS) for plasma t-tau and examined its association with the risk for developing clinical endophenotypes of AD pathology.This longitudinal cohort study used data from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study, involving individuals aged 65 years or older, free of AD, or amnestic mild cognitive impairment (aMCI-an AD prodrome) at baseline. Our primary exposure was PRStau, a PRS based on common genetic variants linked to plasma tau levels. The primary outcome was aMCI or AD incidence. We assessed the association between PRStau levels and aMCI/AD risk using Cox regression models adjusted for age, sex, education, APOE ε4 allele carriership, and population structure. We sought replication in a sample of UK Biobank (UKB) participants aged 60 years or older without prevalent dementia.In the HELIAD sample, among 618 cognitively healthy participants (mean age 73.37 years, 58.4
%K Humans
%K Cognitive Dysfunction: blood
%K Cognitive Dysfunction: genetics
%K Cognitive Dysfunction: epidemiology
%K Aged
%K Female
%K Male
%K Alzheimer Disease: blood
%K Alzheimer Disease: genetics
%K Alzheimer Disease: epidemiology
%K tau Proteins: blood
%K tau Proteins: genetics
%K Longitudinal Studies
%K Multifactorial Inheritance
%K Aged, 80 and over
%K Incidence
%K Biomarkers: blood
%K Risk Factors
%K Middle Aged
%K Cohort Studies
%K Genetic Risk Score
%K tau Proteins (NLM Chemicals)
%K Biomarkers (NLM Chemicals)
%K MAPT protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41043097
%R 10.1212/WNL.0000000000213904
%U https://pub.dzne.de/record/281521