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

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.