Breakpoint sequence analysis of an AβPP locus duplication associated with autosomal dominant Alzheimer's disease and severe cerebral amyloid angiopathy.

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.