Alzheimer’s disease susceptibility gene apolipoprotein e (APOE) and blood biomarkers in UK Biobank (N=395,769)

Ferguson, A. C. et al. (2020) Alzheimer’s disease susceptibility gene apolipoprotein e (APOE) and blood biomarkers in UK Biobank (N=395,769). Journal of Alzheimer's Disease, 76(4), pp. 1541-1551. (doi: 10.3233/JAD-200338) (PMID:32651323)

Abstract

Background: Alzheimer’s disease (AD) is a neurodegenerative condition where the underlying etiology is still unclear. Investigating the potential influence of apolipoprotein E (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk. Objective: Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank. Methods:After quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers. Results: Several biomarkers significantly associated with APOE ɛ4 ‘risk’ and ɛ2 ‘protective’ genotypes (versus neutral ɛ3/ɛ3). Most associations supported previous data: for example, ɛ4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p < 0.001) and ɛ2 with lower LDL (b = –0.456 SDs, p < 0.001). There were however instances of associations found in unexpected directions: e.g., ɛ4 and increased insulin-like growth factor (IGF-1) (b = 0.017, p < 0.001) where lower levels have been previously suggested as an AD risk factor. Conclusion: These findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence herein supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways.

• Item Type: Articles
• Additional Information: UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation. The funders had no role in study design, data collection or management, analyses or interpretation of the data, nor preparation, review or approval of the manuscript. DML is supported by The Neurosciences Foundation, and American Psychological Foundation. Smith is partially funded by the Lister institute. Cavanagh is funded by the Sackler Trust, Wellcome Trust, Medical Research Council, and holds a Wellcome Trust strategic award, an industrial academic collaboration with Janssen & Jannsen, GlaxoSmithKline, and Lundbeck. Pell has received funding from the Medical Research Council and Chief Scientist Office.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ferguson, Ms Amy and Gill, Professor Jason and Ho, Dr Frederick and Mark, Professor Patrick and Smith, Professor Daniel and Welsh, Professor Paul and Anderson, Dr Jana and Lyall, Dr Laura and Ward, Dr Joey and Celis, Dr Carlos and Cavanagh, Professor Jonathan and Tank, Rachana and Pell, Professor Jill and Sattar, Professor Naveed and Strawbridge, Dr Rona and Lyall, Dr Donald
• Authors: Ferguson, A. C., Tank, R., Lyall, L. M., Strawbridge, R., Ward, J., Celis-Morales, C., Ho, F., Whelan, C. D., Gill, J., Welsh, P., Anderson, J. J., Mark, P. B., Smith, D. J., Pell, J. P., Cavanagh, J., Sattar, N., and Lyall, D. M.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > General Practice and Primary Care; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health; College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Journal of Alzheimer's Disease
• Publisher: IOS Press
• ISSN: 1387-2877
• ISSN (Online): 1387-2877
• Copyright Holders: Copyright © IOS Press
• First Published: First published in Journal of Alzheimer's Disease 76(4):1541-1551
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher