Cerebrospinal fluid NPTX2/p-tau ratio as a biomarker for

Authors

Bárbara Fernandes Gomes, Mathias Sauer, Laia Montoliu-Gaya, Maria Franquesa-Mullerat, Alexandre Bejanin, Daniel Alcolea, Alberto Lleó, Ignacio Illán-Gala, Juan Fortea, Kaj Blennow, Henrik Zetterberg, Johanna Nilsson, Olivia Belbin, Nicholas J Ashton

Abstract

Alzheimers Dement (Amst). 2026 Jun 18;18(2):e70391. doi: 10.1002/dad2.70391. eCollection 2026 Apr-Jun.

ABSTRACT

INTRODUCTION: Neuronal pentraxin 2 (NPTX2) and its use as a ratio with other synaptic proteins has emerged as a prognostic cerebrospinal fluid (CSF) biomarker across neurodegenerative diseases.

METHODS: Using a single molecule array (Simoa) method, CSF NPTX2 was measured in 688 individuals from the Sant Pau Initiative on Neurodegeneration, including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal lobar degeneration-related disorders (FTLDrs), and cognitively unimpaired (CU) participants. NPTX2/phosphorylated-tau (p-tau)181 performance was compared to standalone NPTX2 and p-tau181.

RESULTS: The NPTX2/p-tau ratio enhanced diagnostic performance of standalone NPTX2 and p-tau, particularly for DLB and FTLDrs (area under the curve [AUC]_NPTX2/p-tau= 0.78-0.79 vs. AUC_NPTX2= 0.63-0.70 and AUC_p-tau= 0.59-0.75), and was more strongly associated with cognition. It also better predicted progression to dementia across the cohort (hazard ratio [HR] = 1.63), especially in AD (HR = 1.84) and DLB (HR = 1.50).

DISCUSSION: NPTX2/p-tau may improve prognostic assessments in patients with cognitive impairment, outperforming standalone biomarkers.

PMID:42326467 | PMC:PMC13279535 | DOI:10.1002/dad2.70391