Alzheimer's Disease Cerebrospinal Fluid Biomarkers Predict Survival in Progressive Supranuclear Palsy.

BACKGROUND

Alzheimer's disease (AD)-related pathology may co-occur in progressive supranuclear palsy (PSP), although its clinical and prognostic impact is unclear.

OBJECTIVES

To assess whether cerebrospinal fluid (CSF) AD biomarker profiles at diagnosis predict severity and survival in PSP.

METHODS

CSF amyloid-β42 (Aβ42), total and phosphorylated tau (t-tau, p-tau) levels from 85 newly-diagnosed PSP patients and 59 controls were assessed by the amyloid/tau/neurodegeneration (AT[N]) framework, and the p-tau/Aβ42 ratio (AD+ if ≥0.08), and implemented in a survival analysis through Kaplan-Meier, Cox regression, and LASSO-Cox modeling.

RESULTS

AD CSF signature was identified in 5.9% and 18.8% of PSP patients, according to AT(N) and ratio, respectively. It was unrelated to phenotype or severity but strongly predicted survival, with AD+ patients showing markedly shorter survival. The p-tau/Aβ42 ratio was the strongest independent predictor of mortality, together with phenotype and smoking.

CONCLUSIONS

AD-related CSF signature defines a biological PSP subgroup with shortened survival. The p-tau/Aβ42 ratio offers a pragmatic prognostic tool for patient stratification. © 2026 International Parkinson and Movement Disorder Society.