Idiopathic normal-pressure hydrocephalus: pathophysiology and diagnosis by CSF biomarkers.

OBJECTIVES

This observational study aimed to explore the pathophysiology of idiopathic normal-pressure hydrocephalus (iNPH) and to evaluate the diagnostic and prognostic value of CSF biomarkers.

METHODS

Lumbar CSF of patients with iNPH and healthy elderly individuals (HI) and ventricular CSF (VCSF) from the patients with iNPH pre and 6 months postsurgery were analyzed by ELISA. We analyzed neurofilament light protein (NFL), myelin basic protein (MBP), a panel of β-amyloid isoforms (Aβ38, Aβ40, and Aβ42), soluble amyloid precursor protein (sAPP) isoforms sAPPα and sAPPβ, total and phosphorylated tau protein (t- and p-tau), and inflammatory markers interleukin 8, interleukin 10, and monocyte chemoattractant protein 1.

RESULTS

NFL was elevated and amyloid precursor protein (APP)-derived proteins and tau proteins were lower in patients with iNPH than in HI. Postsurgery, there was an increase of NFL, APP-derived proteins, p-tau, and albumin in VCSF, whereas levels of MBP and t-tau had decreased. Improved patients showed a greater increase of APP-derived proteins in VCSF following shunting than did those who did not improve.

CONCLUSIONS

We interpret our data as iNPH pathophysiology to be characterized by a reduced periventricular metabolism and axonal degeneration but no major cortical damage.