Breakpoint Sequence Analysis of an AβPP Locus Duplication Associated with Autosomal Dominant Alzheimer's Disease and Severe Cerebral Amyloid Angiopathy

Article type: Short Communication

Authors: Antonell, Anna^a | Gelpi, Ellen^b | Sánchez-Valle, Raquel^{a; *} | Martínez, Ramiro^c | Molinuevo, José L.^a | Lladó, Albert^a

Affiliations: [a] Alzheimer's Disease and other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain | [b] Neurological Tissue Bank BIOBANK Hospital Clínic-IDIBAPS, Barcelona, Spain | [c] Hospital Mare de Déu de la Mercè, Psicogeriatria, Barcelona, Spain

Correspondence: [*] Correspondence to: Raquel Sánchez-Valle, MD, PhD, Alzheimer's Disease and other Cognitive Disorders Unit, Hospital Clínic, C/Villarroel, 170, 08036 Barcelona, Spain. Tel.: +34 932275785; Fax: +34 932275783; E-mail: rsanchez@clinic.ub.es.

Abstract: AβPP locus duplications have been recently identified in early-onset Alzheimer's disease. We describe a patient who initiated memory problems and behavioral disturbances at 57 years, with a progressive cognitive decline, who died at the age of 68 years with dementia. Neuropathological examination revealed a temporobasal hemorrhage, extensive Alzheimer-type pathology, and severe cerebral amyloid angiopathy. We observed a chromosomal 21 region duplication spanning 0.59 Mb, which comprised JAM2, ATP5J, GABPA, and AβPP genes. We propose a replication based mutational mechanism (single Fork-Stalling and Template-Switching) or a recombination based one (non-homologous end-joining repair) for the AβPP locus duplication in this case.

Keywords: Alzheimer's disease, amyloid-β protein precursor (AβPP), cerebral amyloid angiopathy (CAA), chromosomal duplication, chromosome breakpoint

DOI: 10.3233/JAD-2011-110911

Journal: Journal of Alzheimer's Disease, vol. 28, no. 2, pp. 303-308, 2012