INTRODUCTION

Synaptic dysfunction and loss are pathological hallmarks of neurodegenerative diseases. Neuronal pentraxin 2 (NPTX2), a presynaptic protein involved in synaptic plasticity, has been linked to cognitive decline in Alzheimer's disease (AD) and other neurodegenerative disorders.

METHODS

We developed and validated a novel single molecule array (Simoa) for NPTX2 in cerebrospinal fluid, which was evaluated in two independent cohorts.

RESULTS

CSF NPTX2 concentration was lower (fold change [FC] 0.82, p < 0.01) in AD patients and Down syndrome individuals (FC 0.56, p < 0.001), compared with cognitively unimpaired patients (CU). It was also associated with Mini-Mental State Examination (MMSE) score (β = 2.51, p < 0.001), tau-PET (β = -0.21, p < 0.01), and cortical thickness (β = 0.08, p < 0.001).

DISCUSSION

We describe the first assay for NPTX2 on the Simoa platform, where we continue to highlight the valuable addition of NPTX2 to routine diagnostics of suspected cognitive impairment in patients as it associates better with cognition than other, more established AD biomarkers.

HIGHLIGHTS

Novel method validated for measuring CSF NPTX2 on semi-automated Simoa platform. Method validated for use in CSF, where it shows a significant decrease in both AD and DS patients. Associated with cognition, neurofibrillary tangles, and cortical thickness in AD patients. Associations with cognition are shown to be stronger than those of pTau and NFL.