Cerebrospinal Fluid Amyloid-β Oligomer Levels in Patients with Idiopathic Normal Pressure Hydrocephalus

Abstract

Background:

The amyloid-β oligomers, consisting of 10–20 monomers (AβO ^10–20), have strong neurotoxicity and are associated with cognitive impairment in Alzheimer’s disease (AD). However, their role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood.

Objective:

We hypothesized that cerebrospinal fluid (CSF) AβO ^10–20 accumulates in patients with iNPH, and its clearance after CSF shunting contributes to neurological improvement. We measured CSF AβO ^10–20 levels before and after CSF shunting in iNPH patients evaluating their diagnostic and prognostic role.

Methods:

We evaluated two iNPH cohorts: “evaluation” (cohort-1) with 32 patients and “validation” (cohort-2) with 13 patients. Comparison cohorts included: 27 neurologically healthy controls (HCs), and 16 AD, 15 Parkinson’s disease (PD), and 14 progressive supranuclear palsy (PSP) patients. We assessed for all cohorts CSF AβO ^10–20 levels and their comprehensive clinical data. iNPH cohort-1 pre-shunting data were compared with those of comparison cohorts, using cohort-2 for validation. Next, we compared cohort-1’s clinical and CSF data: 1) before and after CSF shunting, and 2) increased versus decreased AβO ^10–20 levels at baseline, 1 and 3 years after shunting.

Results:

Cohort-1 had higher CSF AβO ^10–20 levels than the HCs, PD, and PSP cohorts. This result was validated with data from cohort-2. CSF AβO ^10–20 levels differentiated cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. AβO ^10–20 levels in cohort-1 decreased after CSF shunting. Patients with AβO ^10–20 decrease showed better cognitive outcome than those without.

Conclusion:

AβO ^10–20 accumulates in patients with iNPH and is eliminated by CSF shunting. AβO ^10–20 can be an applicable diagnostic and prognostic biomarker.