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Review
. 2021 Mar 29:15:650220.
doi: 10.3389/fnins.2021.650220. eCollection 2021.

Polygenic Score Models for Alzheimer's Disease: From Research to Clinical Applications

Xiaopu Zhou  1   2   3 , Yolanda Y T Li  1 , Amy K Y Fu  1   2   3 , Nancy Y Ip  1   2   3
Affiliations
Review

Polygenic Score Models for Alzheimer's Disease: From Research to Clinical Applications

Xiaopu Zhou et al. Front Neurosci. .

Abstract

The high prevalence of Alzheimer's disease (AD) among the elderly population and its lack of effective treatments make this disease a critical threat to human health. Recent epidemiological and genetics studies have revealed the polygenic nature of the disease, which is possibly explainable by a polygenic score model that considers multiple genetic risks. Here, we systemically review the rationale and methods used to construct polygenic score models for studying AD. We also discuss the associations of polygenic risk scores (PRSs) with clinical outcomes, brain imaging findings, and biochemical biomarkers from both the brain and peripheral system. Finally, we discuss the possibility of incorporating polygenic score models into research and clinical practice along with potential challenges.

Keywords: APOE; Alzheimer’s disease; genetics; polygenic hazard score; polygenic risk score; polygenic score; risk prediction.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past collaboration with one of the authors NI.

Figures

FIGURE 1
FIGURE 1
Summary of polygenic score research on Alzheimer’ disease. (A) Numbers of published papers by year. (B) Proportions of studies by population. (C) Proportions of study participants by ethnic group.
FIGURE 2
FIGURE 2
Proposed hierarchal strategy for Alzheimer’s disease risk screening. Individuals enrolled in a screening task are first examined according to genetic risk as indicated by polygenic risk analysis. Individuals who have relatively high risk and report symptoms are referred for biomarker examination to evaluate amyloid-beta, tau (and p-tau), and neurofilament light polypeptide levels (i.e., the “ATN” panel) in blood or cerebrospinal fluid (CSF). Those who exhibit altered levels of biomarkers are further referred to clinicians for cognitive assessment followed by brain imaging including magnetic resonance imaging and positron emission tomography.
See this image and copyright information in PMC

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