Expanding the genomic roadmap of Alzheimer's disease

Alzheimer's disease has a strong heritable component. Early genetic studies of the molecular basis of Alzheimer's disease led to the discovery of rare (less than one per 10 000 population) and highly penetrant mutations in the genes encoding amyloid precursor protein (APP) and presenilin (PSEN1 and PSEN2) in individuals with familial Alzheimer's disease manifesting in a predictable autosomal dominant fashion, usually between the ages of 35 years and 65 years.1 Unlike these mutations, which have a direct effect on the processing of amyloid precursor protein leading to concentrated deposits of toxic amyloid β in the brain, most of the identified genetic variants associated with common late-onset Alzheimer's disease are much more frequent (usually greater than 5% in the general population) and behave as risk modifying, rather than causal, factors.