The Neurobiology and Age-Related Prevalence of the ε4 Allele of Apolipoprotein E in Alzheimer’s Disease Cohorts

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterised by amyloid beta (Aβ) plaques and tau neurofibrillary tangles in the brain. Human apolipoprotein E (ApoE) is a lipid transport protein coded by the polymorphic APOE gene, with three major alleles: ε2, ε3 and ε4. After age, the ε4 allele is the greatest risk factor for developing sporadic AD, conferring an increased risk of 3–4 and 8–12 times for one or two copies of the allele, respectively. This risk is reported to vary by demographic factors including sex, ethnicity and geography. In order to understand the risk of ApoE ε4 in relation to age, the primary risk factor for developing AD, we need to understand how the prevalence of APOE genotypes changes with age. Here, we present the first data on age-related prevalence of APOE ε4 in AD in three AD cohorts in Australia and the USA. There is a significant association between age and ε4 prevalence, particularly for ε4 homozygotes, such that as age increases the prevalence of ε4 decreases. Further studies on a random, population-based sample of the population are needed to provide more generalizable data, particularly in the >90-year-old age group.

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Acknowledgments

The authors gratefully acknowledge Simone Wilk, Chris Fowler and James Doecke for assistance with data retrieval; Oliver Thomas for advice on statistical analysis and Laura Cortes Castrillon for assistance with PyMol. ALH is funded by a Dementia Research Development Fellowship (APP1106911); PP is funded by an Australian Postgraduate Award and an International Postgraduate Research Scholarship. We wish to thank ADNI, AIBL and the National Alzheimer’s Coordinating Centre including all investigators, participants and their families. A complete list of principle investigators and funding sources can be found in the Supplementary Material. The Florey Institute acknowledges the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant.

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The authors declare that they have no conflicts of interest.

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Correspondence to Blaine R. Roberts.

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Heffernan, A.L., Chidgey, C., Peng, P. et al. The Neurobiology and Age-Related Prevalence of the ε4 Allele of Apolipoprotein E in Alzheimer’s Disease Cohorts. J Mol Neurosci 60, 316–324 (2016). https://doi.org/10.1007/s12031-016-0804-x

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Keywords

  • Alzheimer’s disease
  • APOE
  • Apolipoprotein E
  • Population demographics