Corticobasal syndrome (CBS) is a clinically defined syndrome with progressive movement and cortical dysfunction, caused by various underlying pathologies, most commonly tau-predominant pathologies such as progressive supranuclear palsy and corticobasal degeneration, or Alzheimer’s disease (AD). Lewy-type α-synucleinopathies (LTS), TDP-43 proteinopathies, and mixed pathologies may also underlie CBS. The clinical impact of these pathologies remains poorly understood.
Findings revealed a high prevalence of Tau positivity, with 90% of CBS patients being Tau-positive, while Aβ and αSyn positivity were observed in 28% and 24% of cases, respectively. Stratification by biomarker-defined disease entities showed that 52% of CBS cases were consistent with 4RT, 18% with AD, 10% with co-occurrence of AD and LTS, 10% with 4RT and LTS, and 4% with isolated LTS. 6% remained unclassified.
This study underscores the molecular heterogeneity of CBS, highlighting the potential of biomarker-based stratification to improve diagnostic accuracy and guide targeted treatments.