The CSF lipid profile in patients with probable idiopathic normal pressure hydrocephalus differs from control but does not differ between shunt responders and non-responders

Idiopathic normal pressure hydrocephalus is a common form of hydrocephalus in the elderly, characterized by enlarged ventricles combined with clinical symptoms presenting as gait impairment, urinary incontinence, and dementia. Idiopathic normal pressure hydrocephalus may be difficult to differentiate clinically from other neurodegenerative disorders, and up to 80% of cases may remain unrecognized and thus untreated. Consequently, there is a pressing demand for biomarkers that can confirm the diagnosis of idiopathic normal pressure hydrocephalus. In this exploratory study, CSF was sampled from the lumbar compartment of 21 control individuals and 19 probable idiopathic normal pressure hydrocephalus patients and analyzed by an untargeted mass spectroscopy-based platform to reveal a complete CSF lipid profile in these samples. Two hundred forty-four lipids from 17 lipid classes were detected in CSF. Various lipid classes, and select individual lipids, were reduced in the CSF obtained from patients with probable idiopathic normal pressure hydrocephalus, whereas a range of lipids belonging to the class of triacylglycerols was elevated. We detected no difference in the CSF lipid profile between probable idiopathic normal pressure hydrocephalus patients with and without clinical improvement following CSF shunting. In conclusion, the lipidomic profile of the CSF in patients with probable idiopathic normal pressure hydrocephalus, therefore, may serve as a sought after biomarker of the pathology, which may be employed to complement the clinical diagnosis.