Cerebrospinal fluid levels of amyloid-beta oligomers in patients with idiopathic normal pressure hydrocephalus are elevated before shunt surgery but decrease afterward

Abstract Background The amyloid-beta (Aβ) oligomer has strong neurotoxicity and is associated with cognitive impairment in Alzheimer’s disease (AD). However, its role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. We hypothesised that cerebrospinal fluid (CSF) stagnation leads to Aβ oligomer accumulation in patients with iNPH. We measured CSF Aβ oligomer levels before and after CSF shunting in patients with iNPH. Methods We evaluated two iNPH cohorts: an analysis cohort (cohort-1) with 52 patients and a validation cohort (cohort-2) with 13 patients. For comparison cohorts, we recruited 27 neurologically normal controls (NCs), 16 patients with AD, 15 patients with Parkinson’s disease (PD), and 14 patients with progressive supranuclear palsy (PSP). We measured CSF Aβ oligomer levels and assessed participants’ neurological statuses. We then compared the iNPH cohorts’ pre-shunting measurements with the comparison groups’ measurements and compared cohort-1’s measurements recorded before and after CSF shunting. Results iNPH cohort-1 had higher CSF Aβ oligomer levels than the NC, PD, and PSP cohorts. This result was validated with data from iNPH cohort-2. CSF Aβ oligomer levels differentiated iNPH cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. Aβ oligomer levels in iNPH cohort-1 decreased after CSF shunting. However, there was no correlation between Aβ oligomer levels and cognitive functions in iNPH cohort-1. Conclusion The Aβ oligomer accumulates in patients with iNPH patients but can be eliminated with CSF shunting, suggesting that CSF stagnation causes Aβ oligomer accumulation in iNPH.