Alzheimer disease is a progressive, neurodegenerative disease, the prevalence of which increases with age, so that about 25% of people over the age of 85 suffer from this form of senile dementia. Genetic factors are known to be involved in all forms of Alzheimer disease. One of these factors is apolipoprotein E (ApoE), which plays a central role in lipid metabolism.
Two polymorphisms in the APOE gene lead to the amino acid exchanges Cys112Arg (rs429358) and Arg158Cys (rs7412), resulting in the three isoforms ApoE2, ApoE3 and ApoE4 (allele frequency: E2 11%, E3 72% and E4 17%). The APOE4 allele is a risk factor for the late-onset form of Alzheimer disease, and the disease risk and age correlate with the number of APOE4 alleles (gene dose effect). Heterozygosity for the APOE4 allele is associated with an approximately 4-fold increased risk for the late-onset form of Alzheimer disease, homozygosity with an up to 12-fold increased risk. In addition, the average age at onset of the disease is reduced by about 10 years. In contrast, the isoform ApoE2 seems to have a protective effect, so that carriers of the APOE2 allele have a lower risk of disease.
However, APOE genotyping is not suitable for the predictive diagnosis of symptom-free individuals, rather it is exclusively for differential diagnosis and early detection of Alzheimer disease.
Durmaz et al. 2019, Gene pii: S0378-1119(19)30493 / Holtzman et al. 2012, Cold Spring Harb Perspect Med 2:a006312 / Berlau et al. 2009, Neurology 72: 829 / Richard et al. 2009, N Engl J Med 361:255 / Raux et al. 2005, J Med Genet 42:793 / Tanzi et al. 2005, Cell 120:545 / Kowalska et al. 2004, Pol J Pharmacol 56:171 / Casserly et al. 2004, Lancet 363:1139 / Mertens 2002, Dt Ärzteblatt Heft 36 / Esler et Wolfe 2001, Science 293:1449 / Bertram et Tanzi 2001, Curr Neurol Neurosci Rep 1:442 / Li et al. 2000, Nature 405:689