NMDAR subunit GluN1 dynamics in urinary astrocyte-derived extracellular vesicles in anti-NMDAR encephalitis.

BACKGROUND AND

OBJECTIVES

Longitudinal measurement in vivo of molecular changes in the central nervous system (CNS) is important to investigate and guide treatment of rapidly changing neurological diseases. Here, we show how a novel protocol for urinary astrocyte-derived extracellular vesicles (uADEVs) can be used non-invasively to track the dynamic trajectory of the N-methyl-D-aspartate receptor (NMDAR) subunit GluN1 in a patient with anti-NMDAR encephalitis.

METHODS

We collected 18 morning urine samples from the patient over 34 days of hospitalisation, as well as 15 samples from a healthy control. We isolated uADEVs, measured GluN1 concentrations, and used a wavelet transform to analyse the time-frequency dynamics of the GluN1 signal.

RESULTS

Compared with the control, GluN1 levels in the patient's uADEVs were higher on average and more variable over time. Wavelet analysis resolved (i) a low-frequency trend that decreased over time, matching the decrease of GluN1 in cerebrospinal fluid associated with clinical recovery; and (ii) a higher frequency oscillation, with GluN1 levels peaking about 48-72 hours after each of 4 cycles of methotrexate infusion.

CONCLUSION

This case study provides preliminary evidence that urinary ADEV sampling is feasible for measuring brain biomarker dynamics linked to the clinical course and treatment of auto-immune encephalitis.