title: Phenotype associated with APP duplication in five families.
abstract: Different duplications of the APP locus have been identified in five families with autosomal dominant early onset Alzheimer's disease (ADEOAD) and Abeta-related cerebral amyloid angiopathy (CAA). This study describes the phenotype of this new entity. Clinical, neuropsychological, imagery and neuropathological data were reviewed. The phenotype was not dependent on the size of the duplication and there was no clinical feature of Down's syndrome. Dementia was observed in all cases; intracerebral haemorrhage (ICH) was reported in 6 (26%) and seizures occurred in 12 (57%) of 21 patients. Age of onset of dementia ranged from 42 to 59 years, ICH from 53 to 64 years and age at death from 46 to 75 years. The neuropathological findings in five cases demonstrated Alzheimer's disease and severe CAA lesions that were reminiscent from those reported in brains of Down's syndrome patients. A striking feature consisted in intraneuronal Abetax-40 accumulation located in the granular cell layer of the dentate gyrus and in the pyramidal cell layer of the Ammon's horn.
authors.affiliation: Department of Neurology, University Hospital IFRMP, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Cabrejo
authors.forename: Lucie
authors.initials: L
authors.lastname: Guyant-Maréchal
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
authors.forename: Martine
authors.initials: M
authors.lastname: Vercelletto
authors.forename: François
authors.initials: F
authors.lastname: De la Fournière
authors.forename: Catherine
authors.initials: C
authors.lastname: Thomas-Antérion
authors.forename: Christophe
authors.initials: C
authors.lastname: Verny
authors.forename: Franck
authors.initials: F
authors.lastname: Letournel
authors.forename: Florence
authors.initials: F
authors.lastname: Pasquier
authors.forename: Anne
authors.initials: A
authors.lastname: Vital
authors.forename: Frédéric
authors.initials: F
authors.lastname: Checler
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.forename: Dominique
authors.initials: D
authors.lastname: Campion
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D002543:Cerebral Hemorrhage / Q000209:etiology; D004314:Down Syndrome / Q000235:genetics / Q000473:pathology; D005260:Female; D020440:Gene Duplication; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010375:Pedigree; D010641:Phenotype; D014057:Tomography, X-Ray Computed
chemical_list: D016564:Amyloid beta-Protein Precursor