Genetics of Alzheimer's Disease


Knowledge on the genetic aetiology of Alzheimer's disease has greatly increased over the past 20 years. We are now finding that more genetic variants than previously thought play a role in disease susceptibility.

Key Concepts

  • Advances in genetic research into a complex disorder.
  • Alzheimer's disease (AD) is the most common form of dementia and is genetically heterogeneous.
  • The APOE gene has the largest effect size on risk for AD, and is the most replicated finding.
  • Understanding of the genetic risk factors for AD has been greatly increased by advancements in technology.
  • Multiple gene have now been identified as being involved in the aetiology of AD, and have highlight biological pathways that may be affected.
  • Still, these genes do not account for all of the estimated genetic aetiology and therefore variants with even smaller effect size are being investigated through polygenic risk score analysis.

Keywords: Alzheimer's disease; genetics; GWAS; sequencing; polygenic risk score

Figure 1. Schematic of genes associated with Alzheimer's disease indicating their relative effect size against associated variant frequency in the general population. Each gene is colour coded to represent the biological pathway/system it belongs to. Those genes that will be identified by the polygenic risk score are as yet unknown and will demonstrate small effect sizes on the disease manifestation. Adapted from Scheltens et al. 2016 © Elsevier Ltd.


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Further Reading

Metspalu A (2006) Microarrays and Single Nucleotide Polymorphism (SNP) Genotyping (eLS). Chichester: John Wiley & Sons, Ltd.

Reynolds CA (2013) Alzheimer Disease: Genetic and Environmental Influences (eLS). Chichester: John Wiley & Sons, Ltd.

Weiss KM (2017) Allele Spectrum of Human Genetic Disease (eLS), pp. 1–6. Chichester: John Wiley & Sons, Ltd.

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Brookes, Keeley J, and Morgan, Kevin(Dec 2017) Genetics of Alzheimer's Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020228.pub2]