AQP4 levels in CSF correlate with clinical severity in iNPH patients: A pilot study

AQP4 is involved in regulating brain water homeostasis and in the function of the glymphatic system. In iNPH there is an altered parenchymal expression of AQP4, contributing to glymphatic dysfunction. This study aimed to test AQP4 and AQP1 levels in cerebrospinal fluid from iNPH, NOT-NPH, and control subjects to evaluate their diagnostic utility and their correlation with clinical parameters.

CSF samples were collected from probable iNPH patients during the Tap test (TT). Patients who responded to the TT or with a R_out ≥ 12 mmHg/mL/min, performed ventriculoperitoneal shunting (VPS); patients with a negative response to the TT and with a R_out < 12 mmHg/mL/min did not perform surgery (NOT-iNPH group). Ten CSF samples from healthy Controls were collected from our biobank. We conducted an ELISA test to measure levels of Aquaporin 1 and Aquaporin 4. Clinical parameters were collected before and after the TT. A total of 16 iNPH patients, 10 NOT-iNPH patients, and 10 controls were involved in this study.

AQP1 levels were higher in iNPH versus NOT-NPH and controls (p < 0,005); AQP4 levels were similar in the three groups. In iNPH patients only, there was a significant correlation between AQP4 CSF levels and MDS-UPDRS-III (r 0.76, p < 0.001), TUG (Time Up-and-Go) (r 0.58, p < 0.05), and MMSE (r - 0.55, p = 0.05).

AQP-4 CSF levels may correlate with the severity of Parkinsonian signs in iNPH patients, while AQP1 CSF levels may reflect the downregulation of CSF production.