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.
Alzheimer's Disease and other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Anna
A
Antonell
Ellen
E
Gelpi
Raquel
R
Sánchez-Valle
Ramiro
R
Martínez
José L
JL
Molinuevo
Albert
A
Lladó
D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001921:Brain / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000235:genetics / Q000473:pathology; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics*; D013030:Spain; D016875:tau Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D016875:tau Proteins