Development and validation of a novel Simoa assay for NPTX2 in Alzheimer's disease and Down syndrome

TL;DR

A new test for NPTX2 in spinal fluid was developed and shown to be lower in Alzheimer's and Down syndrome patients, and more closely linked to cognitive decline than existing biomarkers.

Contribution

A novel Simoa assay for measuring NPTX2 in cerebrospinal fluid was developed and validated.

Findings

CSF NPTX2 levels were significantly lower in Alzheimer's and Down syndrome patients compared to healthy individuals.

NPTX2 levels correlated with cognitive scores, tau-PET, and cortical thickness in Alzheimer's patients.

NPTX2 showed stronger associations with cognition than pTau and NFL biomarkers.

Abstract

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.

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

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).

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.

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.

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.

Figures