Therefore, there is considerable interest in investigating dominantly-inherited Alzheimer’s disease, which is caused by mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes, and which provides the opportunity to identify asymptomatic ‘at risk’ individuals prior to the onset of cognitive decline for observational studies and clinical trials. Here, PSEN2 is linked to early-onset autosomal dominant Alzheimer disease.