Ventricular volume in relation to lumbar CSF levels of amyloid-β 1-42, tau and phosphorylated tau in iNPH, is there a dilution effect?

Abstract

Background: Levels of the biomarkers amyloid-β 1-42 (Aβ42), tau and phosphorylated tau (p-tau) are decreased in the cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). The mechanism behind this is unknown, but one potential explanation is dilution by excessive CSF volumes. The aim of this study was to investigate the presence of a dilution effect, by studying the relationship between ventricular volume (VV) and the levels of the CSF biomarkers.

Methods: In this cross-sectional observational study, preoperative magnetic resonance imaging (MRI) and lumbar CSF was acquired from 136 patients with a median age of 76 years, 89 men and 47 females, selected for surgical treatment for iNPH. The CSF volume of the lateral and third ventricles was segmented on MRI and related to preoperative concentrations of Aβ42, tau and p-tau.

Results: In the total sample VV (Median 140.7 mL) correlated weakly (r_s = - 0.17) with Aβ42 (Median 534 pg/mL), but not with tau (Median 216 pg/mL) nor p-tau (Median 31 pg/mL). In a subgroup analysis, the correlation between VV and Aβ42 was only present in the male group (r_s = - 0.22, p = 0.038). Further, Aβ42 correlated positively with tau (r_s = 0.30, p = 0.004) and p-tau (r_s = 0.26, p = 0.012) in males but not in females.

Conclusions: The findings did not support a major dilution effect in iNPH, at least not in females. The only result in favor for dilution was a weak negative correlation between VV and Aβ42 but not with the other lumbar CSF biomarkers. The different results between males and females suggest that future investigations of the CSF pattern in iNPH would gain from sex-based subgroup analysis.

Keywords: Amyloid-β; Cerebrospinal fluid; Normal Pressure Hydrocephalus; Tau; Ventricular volume.

Fig. 1

Segmentation example. Example image of the segmentation process using ITK-SNAP. A Axial view of the segmentation. B 3D reconstruction of the segmented volume

Fig. 2

Ventricular Volume and Aβ42 concentration. Scatterplot of ventricular volume Aβ42 concentration for the full sample, n = 136

Fig. 3

Ventricular Volume and Aβ42 concentration in the male subgroup. Scatterplot of ventricular volume Aβ42 concentration for the male subgroup, n = 89

Fig. 4

Ventricular Volume and Aβ42 concentration in the female subgroup. Scatterplot of ventricular volume Aβ42 concentration for the female subgroup, n = 47

Fig. 5

Tau and Aβ42 in the male subgroup. Scatterplot of tau and Aβ42 concentration for the male subgroup, n = 89

Fig. 6

Tau and Aβ42 in the female subgroup. Caption: Scatterplot of tau and Aβ42 concentration for the female subgroup, n = 47