Journal Article

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

Kristel Sleegers, Nathalie Brouwers, Ilse Gijselinck, Jessie Theuns, Dirk Goossens, Jan Wauters, Jurgen Del-Favero, Marc Cruts, Cornelia M. van Duijn and Christine Van Broeckhoven

in Brain

Published on behalf of The Guarantors of Brain

Volume 129, issue 11, pages 2977-2983
ISSN: 0006-8950
Published online August 2006 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awl203
APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy

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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.

Keywords: APP; early onset Alzheimer's disease; genomic duplication

Journal Article.  4238 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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