Alzheimer's Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769).

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  • Additional Information
    • Affiliation:
      Institute of Health and Wellbeing, University of Glasgow, Scotland, UK
      Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK
      GEEAFyS, Universidad Católica del Maule, Talca, Chile
      Health Data Research UK
      Department of Medicine Solna, Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden
      Research and Early Development (RED), Biogen Inc., Cambridge, MA, USA
    • 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 APOEɛ4 '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.
    • Journal Subset:
      Biomedical; Blind Peer Reviewed; Continental Europe; Editorial Board Reviewed; Europe; Expert Peer Reviewed; Peer Reviewed
    • ISSN:
      1387-2877
    • MEDLINE Info:
      PMID: NLM32651323 NLM UID: 9814863
    • Publication Date:
      In Process
    • Publication Date:
      20200925
    • DOI:
      10.3233/JAD-200338
    • Accession Number:
      145184029
  • Citations
    • ABNT:
      FERGUSON, A. C. et al. Alzheimer’s Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769). Journal of Alzheimer’s Disease, [s. l.], v. 76, n. 4, p. 1541–1551, 2020. DOI 10.3233/JAD-200338. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=145184029. Acesso em: 24 out. 2020.
    • AMA:
      Ferguson AC, Tank R, Lyall LM, et al. Alzheimer’s Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769). Journal of Alzheimer’s Disease. 2020;76(4):1541-1551. doi:10.3233/JAD-200338
    • APA:
      Ferguson, A. C., Tank, R., Lyall, L. M., Ward, J., Celis-Morales, C., Strawbridge, R., Ho, F., Whelan, C. D., Gill, J., Welsh, P., Anderson, J. J., Mark, P. B., Mackay, D. F., Smith, D. J., Pell, J. P., Cavanagh, J., Sattar, N., Lyall, D. M., & Beason-Held, L. (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), 1541–1551. https://doi.org/10.3233/JAD-200338
    • Chicago/Turabian: Author-Date:
      Ferguson, Amy C., Rachana Tank, Laura M. Lyall, Joey Ward, Carlos Celis-Morales, Rona Strawbridge, Frederick Ho, 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): 1541–51. doi:10.3233/JAD-200338.
    • Harvard:
      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.
    • Harvard: Australian:
      Ferguson, AC, Tank, R, Lyall, LM, Ward, J, Celis-Morales, C, Strawbridge, R, Ho, F, Whelan, CD, Gill, J, Welsh, P, Anderson, JJ, Mark, PB, Mackay, DF, Smith, DJ, Pell, JP, Cavanagh, J, Sattar, N, Lyall, DM & Beason-Held, L 2020, ‘Alzheimer’s Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769)’, Journal of Alzheimer’s Disease, vol. 76, no. 4, pp. 1541–1551, viewed 24 October 2020, .
    • MLA:
      Ferguson, Amy C., et al. “Alzheimer’s Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769).” Journal of Alzheimer’s Disease, vol. 76, no. 4, Aug. 2020, pp. 1541–1551. EBSCOhost, doi:10.3233/JAD-200338.
    • Chicago/Turabian: Humanities:
      Ferguson, Amy C., Rachana Tank, Laura M. Lyall, Joey Ward, Carlos Celis-Morales, Rona Strawbridge, Frederick Ho, et al. “Alzheimer’s Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769).” Journal of Alzheimer’s Disease 76, no. 4 (August 15, 2020): 1541–51. doi:10.3233/JAD-200338.
    • Vancouver/ICMJE:
      Ferguson AC, Tank R, Lyall LM, Ward J, Celis-Morales C, Strawbridge R, et al. Alzheimer’s Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769). Journal of Alzheimer’s Disease [Internet]. 2020 Aug 15 [cited 2020 Oct 24];76(4):1541–51. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=145184029