Open Access Highly Accessed Research article

Mutation screening of patients with Alzheimer disease identifies APP locus duplication in a Swedish patient

Håkan Thonberg1*, Marie Fallström1, Jenny Björkström1, Jacqueline Schoumans23, Inger Nennesmo4 and Caroline Graff15

Author affiliations

1 Genetics Unit, Dept of Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden

2 Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

3 Cancer Cytogenetic Unit, University Hospital of Lausanne, Switzerland

4 Department of Pathology, Karolinska University Hospital, Huddinge, Sweden

5 Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, KI-Alzheimer Disease Research Center, Stockholm, Sweden

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Citation and License

BMC Research Notes 2011, 4:476  doi:10.1186/1756-0500-4-476

Published: 1 November 2011



Missense mutations in three different genes encoding amyloid-β precursor protein, presenilin 1 and presenilin 2 are recognized to cause familial early-onset Alzheimer disease. Also duplications of the amyloid precursor protein gene have been shown to cause the disease. At the Dept. of Geriatric Medicine, Karolinska University Hospital, Sweden, patients are referred for mutation screening for the identification of nucleotide variations and for determining copy-number of the APP locus.


We combined the method of microsatellite marker genotyping with a quantitative real-time PCR analysis to detect duplications in patients with Alzheimer disease.


In 22 DNA samples from individuals diagnosed with clinical Alzheimer disease, we identified one patient carrying a duplication on chromosome 21 which included the APP locus. Further mapping of the chromosomal region by array-comparative genome hybridization showed that the duplication spanned a maximal region of 1.09 Mb.


This is the first report of an APP duplication in a Swedish Alzheimer patient and describes the use of quantitative real-time PCR as a tool for determining copy-number of the APP locus.