Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Alzheimer's Disease, late onset (AD2) [F00.1]

OMIM numbers: 104310, 107741 (APOE)

Dr. rer. nat. Christoph Marschall, Dipl.-Biol. Christine Schack,
Dipl.-Biol. Christina Sofeso

Scientific Background

Alzheimer's disease is a progressive neurodegenerative disease. The prevalence increases with age so that 25% of those over 85 suffer from this form of senile dementia. Genetic factors are known to be involved in every form of Alzheimer's disease. One of these factors is apolipoprotein E (ApoE), a polymorphic lipoprotein involved in lipid metabolism.

Two polymorphisms in the APOE gene lead to the amino acid substitutions Cys112Arg (rs429358) and Arg158Cys (rs7412), resulting in three isoforms: ApoE2, ApoE3 and ApoE4 (allele frequencies: E2: 11%, E3: 72% and E4: 17%). The APOE4 allele is a risk factor for the late onset form of Alzheimer's disease where the risk of disease and age of onset correlate with the number of APOE4 alleles (gene dose effect). Heterozygosity for the APOE4 allele is associated with a 4 fold elevated risk of developing Alzheimer's disease, homozygosity with a 12 fold elevated risk. In addition, the average age of disease onset is reduced by 10 years. In contrast to this, the ApoE2 isoform seems to have a protective effect as carriers of the APOE2 allele show a lower risk of developing the disease.

However, APOE genotyping is not suited for predictive diagnostics in symptom-free individuals, but only serves in differential diagnosis and early detection of Alzheimer's disease.