We assessed the impact of amyloid precursor protein (APP) gene locus duplications in early onset Alzheimer's disease in a Dutch population-based sample. Using real-time PCR and an in-house-developed multiplex amplicon quantification assay, we identified a genomic APP duplication in 1 out of 10 multigenerational families segregating early onset Alzheimer's disease. In this family, cerebral amyloid angiopathy (CAA) coincided with this disease. The duplicated genomic region included no other genes than APP and extended maximally over 0.7 Mb. In a sample of 65 familial early onset patients, we observed the same APP genomic duplication in one patient (1.7%), while in 36 isolated patients duplications in the APP locus were absent. This indicated that APP locus duplications explained <2% of familial, non-autosomal dominant Alzheimer's disease and are an infrequent cause of de novo mutation. Our findings corroborated a recent French study, and indicated that investigating genomic duplications in the APP locus in families segregating Alzheimer's disease and CAA should be considered.

APP, Early onset Alzheimer's disease, Genomic duplication
dx.doi.org/10.1093/brain/awl203, hdl.handle.net/1765/66273
Brain: a journal of neurology
Erasmus MC: University Medical Center Rotterdam

Sleegers, K, Brouwers, N, Gijselinck, I, Theuns, J, Goossens, D, Wauters, J, … van Broeckhoven, C. (2006). APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy. Brain: a journal of neurology, 129(11), 2977–2983. doi:10.1093/brain/awl203