Brain Metabolic Signatures of Amyloid-β and Tau Pathology in Corticobasal Syndrome: A Multimodal Biomarker Study.

BACKGROUND

Corticobasal syndrome (CBS) may arise from heterogeneous neuropathological substrates, including corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD), and biomarker-based stratification has therefore become central to its characterization in vivo. In a large CBS cohort, we examined whether 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) metabolic patterns reflect underlying amyloid-β deposition and tau topography, and how these patterns relate to the clinical phenotype.

METHODS

We conducted a cross-sectional study of consecutive patients with CBS and were enrolled at Huashan Hospital, Fudan University, between December 2019 and February 2025. Each patient underwent 18F-FDG PET for cerebral glucose metabolism, amyloid status assessment using amyloid PET or cerebrospinal fluid biomarkers, and florzolotau(18F) PET for tau topography.

RESULTS

Among 113 patients, 18F-FDG PET identified five distinct metabolic subgroups: AD type (n = 20), CBD type I (n = 45), CBD type II (n = 18), PSP type (n = 26), and frontotemporal dementia type (n = 4). The AD metabolic pattern showed high specificity for amyloid-β positivity (98.5%) and for combined AD pathology (amyloid-β plus tau, 98.6%), with correspondingly lower sensitivity (54.2% and 72.2%). 18F-FDG PET patterns further showed high specificity for the PSP tau profile (96.2%) and high sensitivity for the CBD tau profile (97.7%). On spatial analysis, amyloid-β deposition significantly mediated the regional coupling between tau accumulation and cerebral glucose hypometabolism.

CONCLUSIONS

18F-FDG PET identifies metabolic patterns that correspond to specific proteinopathies underlying CBS with high specificity but requires integration within multimodal biomarker frameworks for comprehensive patient stratification. © 2026 International Parkinson and Movement Disorder Society.