title: APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy.
abstract: 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.
authors.affiliation: Neurodegenerative Brain Diseases Group Antwerp, Belgium.
authors.forename: Kristel
authors.initials: K
authors.lastname: Sleegers
authors.forename: Nathalie
authors.initials: N
authors.lastname: Brouwers
authors.forename: Ilse
authors.initials: I
authors.lastname: Gijselinck
authors.forename: Jessie
authors.initials: J
authors.lastname: Theuns
authors.forename: Dirk
authors.initials: D
authors.lastname: Goossens
authors.forename: Jan
authors.initials: J
authors.lastname: Wauters
authors.forename: Jurgen
authors.initials: J
authors.lastname: Del-Favero
authors.forename: Marc
authors.initials: M
authors.lastname: Cruts
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D005799:Genes, Dominant; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D016564:Amyloid beta-Protein Precursor