Abstract
We report duplication of the APP locus on chromosome 21 in five families with autosomal dominant early-onset Alzheimer disease (ADEOAD) and cerebral amyloid angiopathy (CAA). Among these families, the duplicated segments had a minimal size ranging from 0.58 to 6.37 Mb. Brains from individuals with APP duplication showed abundant parenchymal and vascular deposits of amyloid-β peptides. Duplication of the APP locus, resulting in accumulation of amyloid-β peptides, causes ADEOAD with CAA.
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Acknowledgements
We thank A. Rossi, C. De La Rochebrochard and H. Moirot for cytogenetic materials, C. Duyckaerts and F. Letournel for brain tissue samples, F. Checler for antibodies to Aβ, J. Bou for technical assistance, A. Goldenberg, S. Jacquemont, E. De La Fournière, T. Dutoya, C. Thomas-Anterion and F. Pasquier for clinical evaluation of patients and M. Tosi for critical reading of the manuscript. A.R.-L. was supported by le Conseil Regional de Haute Normandie.
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Supplementary Fig. 1
QF-PCR analysis. (PDF 596 kb)
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Rovelet-Lecrux, A., Hannequin, D., Raux, G. et al. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 38, 24–26 (2006). https://doi.org/10.1038/ng1718
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DOI: https://doi.org/10.1038/ng1718
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