Characterizing familial corticobasal syndrome due to Alzheimer's disease pathology and PSEN1 mutations

Benjamin Lam; Aun Khan; Julia Keith; Ekaterina Rogaeva; Juan Bilbao; Peter St George-Hyslop; Mahdi Ghani; Morris Freedman; Donald T Stuss; Tiffany Chow; Sandra E Black; Mario Masellis

doi:10.1016/j.jalz.2016.08.014

Characterizing familial corticobasal syndrome due to Alzheimer's disease pathology and PSEN1 mutations

Alzheimers Dement. 2017 May;13(5):520-530. doi: 10.1016/j.jalz.2016.08.014. Epub 2016 Oct 12.

Authors

Affiliations

¹ 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: [email protected].
² Ziauddin University, Karachi, Pakistan.
³ Department of Anatomical Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
⁴ Tanz Centre for Research in Neurodegenerative Disease, Toronto, Ontario, Canada.
⁵ Tanz Centre for Research in Neurodegenerative Disease, Toronto, Ontario, Canada; Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ 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.
¹⁰ 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.

PMID: 27743520
DOI: 10.1016/j.jalz.2016.08.014

Abstract

Introduction: 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.

Discussion: 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.

Keywords: Alzheimer's disease; Corticobasal degeneration; Presenilin-1; SPECT; Volumetric MRI.

MeSH terms

Alzheimer Disease / genetics*
Alzheimer Disease / pathology*
Atrophy / pathology
Autopsy
Brain / pathology
Cerebral Cortex / pathology*
Female
Humans
Magnetic Resonance Imaging / methods
Male
Middle Aged
Mutation
Presenilin-1 / genetics*
Syndrome

Substances

PSEN1 protein, human
Presenilin-1