TY  - JOUR
AU  - Mourtzi, Niki
AU  - Charisis, Sokratis
AU  - Ntanasi, Eva
AU  - Hatzimanolis, Alexandros
AU  - Ramirez, Alfredo
AU  - Sampatakakis, Stefanos N
AU  - Yannakoulia, Mary
AU  - Kosmidis, Mary H
AU  - Dardiotis, Efthimios
AU  - Hadjigeorgiou, George
AU  - Sakka, Paraskevi
AU  - Mamalaki, Eirini
AU  - Papandreou, Christopher
AU  - Georgakis, Marios K
AU  - Scarmeas, Nikolaos
TI  - Longitudinal Association of a Polygenic Risk Score for Plasma T-Tau With Incident Alzheimer Dementia and Mild Cognitive Impairment.
JO  - Neurology
VL  - 105
IS  - 9
SN  - 0028-3878
CY  - Philadelphia, Pa.
PB  - Wolters Kluwer
M1  - DZNE-2025-01139
SP  - e213904
PY  - 2025
AB  - 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
KW  - Humans
KW  - Cognitive Dysfunction: blood
KW  - Cognitive Dysfunction: genetics
KW  - Cognitive Dysfunction: epidemiology
KW  - Aged
KW  - Female
KW  - Male
KW  - Alzheimer Disease: blood
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: epidemiology
KW  - tau Proteins: blood
KW  - tau Proteins: genetics
KW  - Longitudinal Studies
KW  - Multifactorial Inheritance
KW  - Aged, 80 and over
KW  - Incidence
KW  - Biomarkers: blood
KW  - Risk Factors
KW  - Middle Aged
KW  - Cohort Studies
KW  - Genetic Risk Score
KW  - tau Proteins (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - MAPT protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41043097
DO  - DOI:10.1212/WNL.0000000000213904
UR  - https://pub.dzne.de/record/281521
ER  -