Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer's Disease.

Loading...
Thumbnail Image

Date

2021-10-13

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

64
views
72
downloads

Citation Stats

Abstract

Mild cognitive impairment (MCI) is a heterogeneous condition and MCI patients are at increased risk of progression to dementia due to Alzheimer's disease (AD). In this study, we aim to evaluate the associations between polygenic risk scores (PRSs) and 1) time to AD progression from MCI, 2) changes in longitudinal cognitive impairment, and 3) biomarkers from cerebrospinal fluid and imaging. We constructed PRS by using 40 independent non-APOE SNPs from well-replicated AD GWASs and tested its association with the progression time from MCI to AD by using 767 MCI patients from the ADNI study and 1373 patients from the NACC study. PRSs calculated with other methods were also computed. We found that the PRS constructed with SNPs that reached genome-wide significance predicted the progression from MCI to AD (beta = 0.182, se = 0.061, p = 0.003) after adjusting for the demographic and clinical variables. This association was replicated in the NACC dataset (beta = 0.094, se = 0.037, p = 0.009). Further analyses revealed that PRS was associated with the increased ADAS-Cog11/ADAS-Cog13/ADASQ4 scores, tau/ptau levels, and cortical amyloid burdens (PIB and AV45), but decreased hippocampus and entorhinal cortex volumes (p <  0.05). Mediation analysis showed that the effect of PRS on the increased risk of AD may be mediated by Aβ 42 (beta = 0.056, SE = 0.026, p = 0.036). Our findings suggest that PRS can be useful for the prediction of time to AD and other clinical changes after the diagnosis of MCI.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.3233/jad-210700

Publication Info

Liu, Hongliang, Michael Lutz, Sheng Luo and undefined Alzheimer’s Disease Neuroimaging Initiative (2021). Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer's Disease. Journal of Alzheimer's disease : JAD. pp. 1–13. 10.3233/jad-210700 Retrieved from https://hdl.handle.net/10161/23954.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Lutz

Michael William Lutz

Professor in Neurology

Developing and using computational biology methods to understand the genetic basis of disease with a focus on Alzheimer’s Disease.   Recent work has focused on identification and validation of clinically-relevant biomarkers for Alzheimer’s disease and Alzheimer’s disease with Lewy bodies.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.