Brain scans reveal hidden diversity in rare movement disorder
A new study finds that corticobasal syndrome, a progressive neurological disorder, stems from six distinct underlying causes—most commonly tau buildup but also Alzheimer's disease and other pathologies. The discovery could reshape how doctors diagnose and treat the condition, potentially unlocking targeted therapies for a disease previously treated as one-size-fits-all.
Originaltitel: A Biomarker-Based Classification of Corticobasal Syndrome
Background 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 alpha-synucleinopathies (LTS), TDP-43 proteinopathies, and mixed pathologies may also underlie CBS. The clinical impact of these pathologies remains poorly understood. Objectives To subclassify CBS patients in vivo using biomarkers for amyloid-beta (A beta), Tau, and alpha-synuclein (alpha Syn), and assess the clinical relevance of this stratification. Methods We conducted a prospective cohort study of 50 CBS patients at LMU University Hospital Munich. Biomarker analysis included cerebrospinal fluid (CSF) A beta 42 and A beta 42/40, [18F]flutemetamol A beta-PET, [18F]PI-2620 tau-PET, and alpha Syn seed amplification assays in CSF. CSF neurofilament light chain (NfL) served as a marker of neurodegeneration. Patients were stratified into six groups based on biomarker positivity. Results Tau positivity was found in 90% of CBS cases, A beta in 28%, and alpha Syn in 24%. Stratification identified: 52% consistent with tau-predominant pathology, 18% with AD, 10% with AD+LTS, 10% with tau-predominant+LTS, 4% with isolated LTS, and 6% unclassified. alpha Syn positivity was more frequent in AD-CBS (36%) than in tau-predominant-CBS (16%). A beta-positive cases showed greater cognitive impairment; Tau positivity correlated with worse motor symptoms; alpha Syn-positive patients had milder motor symptoms, slower progression, and lower NfL levels. Conclusions CBS is molecularly heterogeneous. Biomarker-based classification may enhance diagnostic precision and support personalized therapeutic strategies. (c) 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.