Background: Alzheimer's disease is the most frequent cause of dementia. Recent knowledge reveals several new risk genes. We wish to summarise the knowledge of genetic factors related to Alzheimer's disease.
Method: This article is based on findings in Alzgene, a database that summarises genetic association studies in Alzheimer's disease, a literature search in PubMed and the authors' own experience in dementia research.
Results: Several mutations of the genes APP, PSEN1 and PSEN2 are described. These cause around half of all cases of the rare early onset autosomal dominant form of Alzheimer's disease. Heritability, or how much of the development of the disease in an individual that is explained by genetics, is between 60 and 80% in the most common late onset form of Alzheimer's disease. APOE ε4 is the most robust risk gene for the development of this form of the disease, but recently ten new genes that increase the risk of developing Alzheimer's disease were identified by applying genome-wide association studies. These genes code for proteins that are central in the metabolism of cholesterol, activation of the immune system and synaptic cell membrane processes.
Interpretation: New hypotheses on the disease mechanisms for Alzheimer's disease are suggested based on the identification of new risk genes. These hypotheses partly replace and partly supplement the previously dominant amyloid pathway hypothesis. The new risk genes point to the potential for new biomarkers for specific disease processes and to possible new targets for future disease modifying therapies.