Association between p-tau181 in cerebrospinal fluid and shunt response in patients with normal-pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a treatable condition, but predicting shunt response remains challenging. Cerebrospinal fluid (CSF) biomarkers, including phosphorylated tau (p-tau181), have been suggested as potential predictors, although existing evidence is inconsistent.

In this retrospective single-center study, we included 230 patients with probable or possible iNPH who underwent shunt surgery and had available CSF biomarker data for Amyloid beta42, total tau and phosphorylated tau 181. Patients were divided into two cohorts based on assay method (Innotest^® and Elecsys^®). The primary outcome was improvement in gait score. Secondary outcomes included cognition, continence, and overall clinical response. Predictive performance of CSF p-tau181 was evaluated using logistic regression and receiver operating characteristic (ROC) analyses.

Mean CSF p-tau181 levels did not differ significantly between responders and non-responders in either cohort. In multivariable logistic regression analyses adjusted for age and sex, CSF p-tau181 was not associated with shunt response (Innotest^®: OR 0.997 (0.972-1.024), p = 0.815; Elecsys^®: OR 1.091 (0.910-1.419), p = 0.429). Findings were consistent across two CSF p-tau181 assay platforms, although the Elecsys^® cohort was underpowered for calculating AUC with only 14 non-responders. Similar results were observed across secondary outcomes and after exclusion of patients with high CSF p-tau181 levels to reduce potential confounding by concomitant Alzheimer's disease pathology.

CSF p-tau181 does not demonstrate clinically meaningful predictive value for shunt response in patients with iNPH and cannot alone guide patient selection for shunt surgery. Future research should focus on multimodal approaches integrating clinical, radiological, and biochemical markers.