ApoE in Alzheimer's disease

Apolipoprotein E4 confers a dose-related risk for developing Alzheimer's disease.

There is experimental evidence which permits estimation of the size of the risk:

• the possession of apoE4 confers a 2.27 fold relative risk for Alzheimer's disease over homozygotes for the common apoE3 polymorphism
  
  
• the increased risk is only significant for patients presenting between the ages of 60 and 70; in older patients, representing 60% of cases, apoE4 is not a risk factor for Alzheimer's disease
  
  
• homozygosity for apoE4 is a greater risk than heterozygosity; despite this a survey of apoE4 homozygotes with an average age of 81 demonstrated that 85% were unimpaired on mental status tests
  
  
• APOE4 allele remains the strongest genetic risk factor for sporadic Alzheimer's disease and the APOE2 allele the strongest genetic protective factor after multiple large scale genome-wide association studies and genome-wide association meta-analyses (4)

Reference:

• 1) Evans, DA, Beckett, LA, Field, TS et al. (1997) Apolipoprotein E4 and incidence of Alzheimer's disease in a community population of older persons. JAMA, 277,822.
• 2) Blacker, D, Haines, JL, Rodes, L et al. (1997) APOE-4 and age of onset of Alzheimer's disease: the NIMH genetics initiative. Neurology, 48, 139.
• 3) Hyman, BT, Gomez-Isla, T, Brigg, M. et al. (1996) Apolipoprotein E4 and cognitive change in an elderly population. Ann Neurol, 40, 55.
• 4) Kunkle BW et al.Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing.Nat Genet. 2019; 51: 414-430