title: APP Mutations in Cerebral Amyloid Angiopathy with or without Cortical Calcifications: Report of Three Families and a Literature Review.
abstract: Specific APP mutations cause cerebral amyloid angiopathy (CAA) with or without Alzheimer's disease (AD).
  
  
  
  We aimed at reporting APP mutations associated with CAA, describe the clinical, cerebrospinal fluid AD biomarkers, and neuroimaging features, and compare them with the data from the literature.
  
  
  
  We performed a retrospective study in two French genetics laboratories by gathering all clinical and neuroimaging data from patients referred for a genetic diagnosis of CAA with an age of onset before 66 years and fulfilling the other Boston revised criteria. We studied the segregation of mutations in families and performed a comprehensive literature review of all cases reported with the same APP mutation.
  
  
  
  We screened APP in 61 unrelated French patients. Three mutations, located in the Aβ coding region, were detected in five patients from three families: p.Ala692Gly (Flemish), p.Glu693Lys (Italian), and p.Asp694Asn (Iowa). Patients exhibited CAA and progressive cognitive impairment associated with cortical calcifications in the Iowa and Italian mutation carriers, but not the patient carrying the Flemish mutation.
  
  
  
  This is the first evidence of cortical calcification in patients with an APP mutation other than the Iowa mutation. We discuss the radiological, cerebrospinal fluid, and clinical phenotype of patients carrying these mutations in the literature.
authors.affiliation: Department of Neurology and Consultation Mémoire de Ressource et de Recherche, Hôpitaux Civils de Colmar, Colmar, France.|Strasbourg University, INSERM U-1118, Faculty of Medicine, Strasbourg, France.
authors.forename: François
authors.initials: F
authors.lastname: Sellal
authors.affiliation: Department of Neurology, Rouen University Hospital, Rouen, France.|CNR-MAJ, Rouen University Hospital, Rouen, France.|Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Center for Genomic and Personalized Medicine, Rouen, France.
authors.forename: David
authors.initials: D
authors.lastname: Wallon
authors.affiliation: Neurology Department, Centre Hospitalier, Aix-en-Provence, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Martinez-Almoyna
authors.affiliation: Service de Neurologie, CMRR, CHRU Gui de Chauliac, Montpellier, France.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marelli
authors.affiliation: Radiology Service, Hospital of Moenchsberg, Mulhouse, France.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Dhar
authors.affiliation: Radiology Service, Hospital of Moenchsberg, Mulhouse, France.
authors.forename: Héléne
authors.initials: H
authors.lastname: Oesterlé
authors.affiliation: Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Center for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Rovelet-Lecrux
authors.affiliation: CNR-MAJ, Rouen University Hospital, Rouen, France.|Normandy Center for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Rousseau
authors.affiliation: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, USA.|Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston, USA.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Kourkoulis
authors.affiliation: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, USA.|Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Rosand
authors.affiliation: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, USA.|Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston, USA.
authors.forename: Zora Y
authors.initials: ZY
authors.lastname: DiPucchio
authors.affiliation: Neuropathology Service, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Frosch
authors.affiliation: Neurology Department, Centre Hospitalier, Aix-en-Provence, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Gombert
authors.affiliation: Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Audoin
authors.affiliation: AP-HP, Service de génétique moléculaire neurovasculaire, Hôpital Lariboisiére, Paris, France.|Inserm, U1161, Université Paris 7 Diderot, Paris, France.
authors.forename: Manuèle
authors.initials: M
authors.lastname: Miné
authors.affiliation: AP-HP, Service de génétique moléculaire neurovasculaire, Hôpital Lariboisiére, Paris, France.|Inserm, U1161, Université Paris 7 Diderot, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Riant
authors.affiliation: Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Center for Genomic and Personalized Medicine, Rouen, France.|Department of Genetics, Rouen University Hospital, Rouen, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.affiliation: Department of Neurology, Rouen University Hospital, Rouen, France.|CNR-MAJ, Rouen University Hospital, Rouen, France.|Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Center for Genomic and Personalized Medicine, Rouen, France.|Department of Genetics, Rouen University Hospital, Rouen, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
authors.affiliation: CNR-MAJ, Rouen University Hospital, Rouen, France.|Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Center for Genomic and Personalized Medicine, Rouen, France.|Department of Research, Rouvray Psychiatric Hospital, Sotteville-Lés-Rouen, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Campion
authors.affiliation: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, USA.|Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
authors.affiliation: AP-HP, Service de génétique moléculaire neurovasculaire, Hôpital Lariboisiére, Paris, France.|Inserm, U1161, Université Paris 7 Diderot, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Tournier-Lasserve
authors.affiliation: CNR-MAJ, Rouen University Hospital, Rouen, France.|Inserm U1079, Rouen University, IRIB, Normandy University, Rouen, France.|Normandy Center for Genomic and Personalized Medicine, Rouen, France.|Department of Genetics, Rouen University Hospital, Rouen, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Nicolas
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D002114:Calcinosis / Q000209:etiology / Q000235:genetics*; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000235:genetics*; D002540:Cerebral Cortex / Q000473:pathology*; D005192:Family Health; D006801:Humans; D009154:Mutation / Q000235:genetics*
chemical_list: D016564:Amyloid beta-Protein Precursor
keywords: APP; Alzheimer’s disease; amyloid-β; calcification; cerebral amyloid angiopathy; mutation