title: Characterizing familial corticobasal syndrome due to Alzheimer's disease pathology and PSEN1 mutations.
abstract: BACKGROUND
  Corticobasal syndrome (CBS) resulting from genetic Alzheimer's disease (AD) has been described only once. Whether familial CBS-AD is a distinct clinical entity with its own imaging signature remains unknown.
  
  
  METHODS
  Four individuals with CBS from two families underwent detailed assessment. For two individuals, regional atrophy and hypoperfusion were compared to autopsy-confirmed typical late-onset AD and corticobasal degeneration, as well as genetically proven PSEN1 cases with an amnestic presentation.
  
  
  RESULTS
  One family harbored a novel mutation in PSEN1:p.Phe283Leu. MRI demonstrated severe parietal, perirolandic, and temporal atrophy, with relative sparing of frontal and ipsilateral hippocampal regions. Autopsy confirmed pure AD pathology. The other family harbored a known PSEN1 mutation:p.Gly378Val.
  
  
  CONCLUSIONS
  This report confirms familial CBS-AD as a distinct clinical entity, with a parietal-perirolandic-temporal atrophy signature. It illustrates the clinical heterogeneity that can occur despite a shared genetic cause and underscores the need for biomarkers such as amyloid imaging during life.
authors.affiliation: L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: benjamin.lam@sunnybrook.ca.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lam
authors.affiliation: Ziauddin University, Karachi, Pakistan.
authors.forename: Aun
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Anatomical Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Julia
authors.initials: J
authors.lastname: Keith
authors.affiliation: Tanz Centre for Research in Neurodegenerative Disease, Toronto, Ontario, Canada.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Rogaeva
authors.affiliation: Department of Anatomical Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: Bilbao
authors.affiliation: Tanz Centre for Research in Neurodegenerative Disease, Toronto, Ontario, Canada; Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: St George-Hyslop
authors.affiliation: Tanz Centre for Research in Neurodegenerative Disease, Toronto, Ontario, Canada.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Ghani
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Sam and Ida Ross Memory Clinic, Baycrest, Toronto, Ontario, Canada; Rotman Research Institute, Baycrest, University of Toronto, Toronto, Ontario, Canada; Toronto Dementia Research Alliance, Toronto, Ontario, Canada.
authors.forename: Morris
authors.initials: M
authors.lastname: Freedman
authors.affiliation: Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Rotman Research Institute, Baycrest, University of Toronto, Toronto, Ontario, Canada; Department of Psychology, University of Toronto, Toronto, Ontario, Canada; Ontario Brain Institute, Toronto, Ontario, Canada.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Stuss
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Sam and Ida Ross Memory Clinic, Baycrest, Toronto, Ontario, Canada; Rotman Research Institute, Baycrest, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Chow
authors.affiliation: L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Rotman Research Institute, Baycrest, University of Toronto, Toronto, Ontario, Canada; Toronto Dementia Research Alliance, Toronto, Ontario, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.affiliation: L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Toronto Dementia Research Alliance, Toronto, Ontario, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Masellis
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001284:Atrophy / Q000473:pathology; D001344:Autopsy; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053764:Presenilin-1 / Q000235:genetics*; D013577:Syndrome
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: Alzheimer's disease; Corticobasal degeneration; Presenilin-1; SPECT; Volumetric MRI