PSEN1

About PSEN1

PSEN1 on chromosome 14q24.2 encodes presenilin 1, the catalytic component of the gamma secretase complex that cleaves amyloid precursor protein and many other membrane proteins, including Notch receptors. Variants in PSEN1 are the most common known cause of early onset autosomal dominant Alzheimer disease, with hundreds of different variants described. These variants typically shift amyloid beta production toward longer, more aggregation prone forms, and symptoms often begin between the ages of thirty and fifty. A large extended family in Antioquia, Colombia, carrying the E280A variant has been central to research on the earliest stages of the disease and to prevention trials. A related gene, PSEN2 on chromosome 1, causes a smaller number of familial cases. Because PSEN1 variants are highly penetrant, predictive testing is usually offered only with genetic counselling.