Document Type

Journal Article

Publication Title

Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

Publisher

Wiley

School

School of Medical and Health Sciences / Centre for Precision Health

RAS ID

36631

Funders

Funding information available in the Acknowledgements section of the PDF

Comments

Huq, A. J., Fulton‐Howard, B., Riaz, M., Laws, S., Sebra, R., Ryan, J., ... & Lacaze, P. (2021). Polygenic score modifies risk for Alzheimer's disease in APOE ε4 homozygotes at phenotypic extremes. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 13(1), e12226. https://doi.org/10.1002/dad2.12226

Abstract

Introduction: Diversity in cognition among apolipoprotein E () ε4 homozygotes can range from early-onset Alzheimer's disease (AD) to a lifetime with no symptoms. Methods: We evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy ε4 homozygotes aged ≥75 years (n = 213) and early-onset ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity. Results: The PRS for AD was significantly higher in ε4 homozygote AD cases compared to older cognitively healthy ε4/ε4 controls (odds ratio [OR] 8.39; confidence interval [CI] 2.0-35.2; = .003). The difference in the same PRS between ε3/ε3 extremes was not as significant (OR 3.13; CI 0.98-9.92; = .053) despite similar numbers and power. There was no statistical difference in an educational attainment PRS between these age extreme case-controls. Discussion: A PRS for AD contributes to modified cognitive expression of the ε4/ε4 genotype at phenotypic extremes of risk.

DOI

10.1002/dad2.12226

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Research Themes

Health

Priority Areas

Neuroscience and neurorehabilitation

Included in

Neurosciences Commons

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