Effects of Alzheimer's Disease-Associated Risk Loci on Cerebrospinal Fluid Biomarkers and Disease Progression: A Polygenic Risk Score Approach

2014 ◽  
Vol 43 (2) ◽  
pp. 565-573 ◽  
Author(s):  
Henna Martiskainen ◽  
Seppo Helisalmi ◽  
Jayashree Viswanathan ◽  
Mitja Kurki ◽  
Anette Hall ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Disease Progression ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Cerebrospinal Fluid Biomarkers

scholarly journals Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jung-Min Pyun ◽  
Young Ho Park ◽  
Keon-Joo Lee ◽  
SangYun Kim ◽  
Andrew J. Saykin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Disease Progression ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Carrier Status ◽  
Polygenic Risk ◽  
Increased Risk

Abstract Background The combinatorial effect of multiple genetic factors calculated as a polygenic risk score (PRS) has been studied to predict disease progression to Alzheimer’s disease (AD) from mild cognitive impairment (MCI). Previous studies have investigated the performance of PRS in the prediction of disease progression to AD by including and excluding single nucleotide polymorphisms within the region surrounding the APOE gene. These studies may have missed the APOE genotype-specific predictability of PRS for disease progression to AD. Methods We analyzed 732 MCI from the Alzheimer’s Disease Neuroimaging Initiative cohort, including those who progressed to AD within 5 years post-baseline (n = 270) and remained stable as MCI (n = 462). The predictability of PRS including and excluding the APOE region (PRS+APOE and PRS−APOE) on the conversion to AD and its interaction with the APOE ε4 carrier status were assessed using Cox regression analyses. Results PRS+APOE (hazard ratio [HR] 1.468, 95% CI 1.335–1.615) and PRS−APOE (HR 1.293, 95% CI 1.157–1.445) were both associated with a significantly increased risk of MCI progression to dementia. The interaction between PRS+APOE and APOE ε4 carrier status was significant with a P-value of 0.0378. The association of PRSs with the progression risk was stronger in APOE ε4 non-carriers (PRS+APOE: HR 1.710, 95% CI 1.244–2.351; PRS−APOE: HR 1.429, 95% CI 1.182–1.728) than in APOE ε4 carriers (PRS+APOE: HR 1.167, 95% CI 1.005–1.355; PRS−APOE: HR 1.172, 95% CI 1.020–1.346). Conclusions PRS could predict the conversion of MCI to dementia with a stronger association in APOE ε4 non-carriers than APOE ε4 carriers. This indicates PRS as a potential genetic predictor particularly for MCI with no APOE ε4 alleles.

P4-240: Using polygenic risk score to predict Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_19) ◽  
pp. P872-P872 ◽  
Author(s):  
Valentina Escott-Price ◽  
Rebecca Sims ◽  
Denise Harold ◽  
Maria Vronskaya ◽  
Peter Holmans ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk

P3-077: ALZHEIMER'S DISEASE (AD) POLYGENIC RISK SCORE (PRS) AS A PREDICTOR OF CONVERSION FROM MILD COGNITIVE IMPAIRMENT (MCI)

2006 ◽  
Vol 14 (7S_Part_20) ◽  
pp. P1094-P1094
Author(s):  
Sultan Raja Chaudhury ◽  
Tulsi Patel ◽  
Abigail Fallows ◽  
Keeley J. Brookes ◽  
Tamar Guetta-Baranes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals POLYGENIC RISK SCORE ANALYSIS OF ALZHEIMER’S DISEASE IN CASES WITHOUT APOE4 OR APOE2 ALLELES

2018 ◽  
pp. 1-4
Author(s):  
V. Escott-Price ◽  
A. Myers ◽  
M. Huentelman ◽  
M. Shoai ◽  
J. Hardy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Score ◽  
Clinical Trial Design ◽  
Polygenic Risk Score ◽  
Carrier Status ◽  
Predictive Utility ◽  
Polygenic Risk ◽  
Score Analysis ◽  
E4 Allele

The We and others have previously shown that polygenic risk score analysis (PRS) has considerable predictive utility for identifying those at high risk of developing Alzheimer’s disease (AD) with an area under the curve (AUC) of >0.8. However, by far the greatest determinant of this risk is the apolipoprotein E locus with the E4 allele alone giving an AUC of ~0.68 and the inclusion of the protective E2 allele increasing this to ~0.69 in a clinical cohort. An important question is to determine how good PRS is at predicting risk in those who do not carry the E4 allele (E3 homozygotes, E3E2 and E2E2) and in those who carry neither the E4 or E2 allele (i.e. E3 homozygotes). Previous studies have shown that PRS remains a significant predictor of AD risk in clinical cohorts after controlling for APOE ε4 carrier status. In this study we assess the accuracy of PRS prediction in a cohort of pathologically confirmed AD cases and controls. The exclusion of APOE4 carriers has surprisingly little effect on the PRS prediction accuracy (AUC ~0.83 [95% CI: 0.80-0.86]), and the accuracy remained higher than that in clinical cohorts with APOE included as a predictor. From a practical perspective this suggests that PRS analysis will have predictive utility even in E4 negative individuals and may be useful in clinical trial design.

scholarly journals Use of an Alzheimer’s disease polygenic risk score to identify mild cognitive impairment in adults in their 50s

2018 ◽  
Vol 24 (3) ◽  
pp. 421-430 ◽  
Author(s):  
Mark W. Logue ◽  
Matthew S. Panizzon ◽  
Jeremy A. Elman ◽  
Nathan A. Gillespie ◽  
Sean N. Hatton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals The Correlation between Inflammatory Biomarkers and Polygenic Risk Score in Alzheimer’s Disease

2017 ◽  
Vol 56 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Angharad R. Morgan ◽  
Samuel Touchard ◽  
Caroline O’Hagan ◽  
Rebecca Sims ◽  
Elisa Majounie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Score ◽  
Inflammatory Biomarkers ◽  
Polygenic Risk Score ◽  
Polygenic Risk
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