APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy

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...

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Bibliographic Details
Published in:Brain (London, England : 1878) England : 1878), 2006-11, Vol.129 (11), p.2977-2983
Main Authors: Sleegers, Kristel, Brouwers, Nathalie, Gijselinck, Ilse, Theuns, Jessie, Goossens, Dirk, Wauters, Jan, Del-Favero, Jurgen, Cruts, Marc, Duijn, Cornelia M. van, Broeckhoven, Christine Van
Format: Article
Language:English
Subjects:
Adult
Age of Onset
Aged
Alzheimer Disease - complications
Alzheimer Disease - genetics
Amyloid beta-Protein Precursor - genetics
APP
Biological and medical sciences
Cerebral Amyloid Angiopathy - complications
Cerebral Amyloid Angiopathy - genetics
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Dementia
early onset Alzheimer's disease
Female
Gene Duplication
Genes, Dominant
genomic duplication
Humans
In Situ Hybridization, Fluorescence
Male
Medical sciences
Middle Aged
Neurology
Pedigree
Polymerase Chain Reaction - methods
Vascular diseases and vascular malformations of the nervous system
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Summary: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
ISSN:0006-8950
1460-2156
DOI:10.1093/brain/awl203