Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's Disease Neuroimaging Initiative



: Zettergren Anne, Lord Jodie, Ashton Nicholas J, Benedet Andrea L, Karikari Thomas K, Lantero Rodriguez Juan, Snellman Anniina, Suárez-Calvet Marc, Proitsi Petroula, Zetterberg Henrik, Blennow Kaj

: 2021

: Alzheimer's Research and Therapy

: Alzheimer's research & therapy

: Alzheimers Res Ther

: 17

: 13

: 1758-9193

DOI: https://doi.org/10.1186/s13195-020-00754-8

: https://research.utu.fi/converis/portal/detail/Publication/51386336


Polygenic risk for AD including APOE was found to associate with plasma p-tau181 independent of diagnostic and Aβ pathology status, while polygenic risk for AD beyond APOE was associated with plasma p-tau181 only in MCI and Aβ-positive individuals. These results extend the knowledge about the relation between genetic risk for AD and p-tau181, and further support the usefulness of plasma p-tau181 as a biomarker of AD.\nRecent studies suggest that plasma phosphorylated tau181 (p-tau181) is a highly specific biomarker for Alzheimer's disease (AD)-related tau pathology. It has great potential for the diagnostic and prognostic evaluation of AD, since it identifies AD with the same accuracy as tau PET and CSF p-tau181 and predicts the development of AD dementia in cognitively unimpaired (CU) individuals and in those with mild cognitive impairment (MCI). Plasma p-tau181 may also be used as a biomarker in studies exploring disease pathogenesis, such as genetic or environmental risk factors for AD-type tau pathology. The aim of the present study was to investigate the relation between polygenic risk scores (PRSs) for AD and plasma p-tau181.\nData from the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used to examine the relation between AD PRSs, constructed based on findings in recent genome-wide association studies, and plasma p-tau181, using linear regression models. Analyses were performed in the total sample (n = 818), after stratification on diagnostic status (CU (n = 236), MCI (n = 434), AD dementia (n = 148)), and after stratification on Aβ pathology status (Aβ positives (n = 322), Aβ negatives (n = 409)).\n), while the non-APOE PRSs were associated with plasma p-tau181 in Aβ positives only (p = 0.02).\nCONCLUSIONS\nBACKGROUND\nMETHODS\nRESULTS

Last updated on 2024-26-11 at 22:24