Circulating neurofilament is linked with morbid obesity, renal function, and brain density

Abstract

Neurofilament light chain (NfL) is a novel biomarker reflecting neuroaxonal damage and associates with brain atrophy, and glial fibrillary acidic protein (GFAP) is a marker of astrocytic activation, associated with several neurodegenerative diseases. Since obesity is associated with increased risk for several neurodegenerative disorders, we hypothesized that circulating NfL and GFAP levels could reflect neuronal damage in obese patients. 28 morbidly obese and 18 lean subjects were studied with voxel based morphometry (VBM) MRI to assess gray and white matter densities. Serum NfL and GFAP levels were determined with single-molecule array. Obese subjects were re-studied 6 months after bariatric surgery. Morbidly obese subjects had lower absolute concentrations of circulating NfL and GFAP compared to lean individuals. Following bariatric surgery-induced weight loss, both these levels increased. Both at baseline and after weight loss, circulating NfL and GFAP values correlated inversely with eGFR. Cross-sectionally, circulating NfL levels correlated inversely with gray matter (GM) density, and this association remained significant also when accounting for age and total eGFR. GFAP values did not correlate with GM density. Our data suggest that when determining circulating NfL and GFAP levels, eGFR should also be measured since renal function can affect these measurements. Despite the potential confounding effect of renal function on NfL measurement, NfL correlated inversely with gray matter density in this group of subjects with no identified neurological disorders, suggesting that circulating NfL level may be a feasible biomarker of cerebral function even in apparently neurologically healthy subjects.

Figure 1

Plasma NfL levels correlated positively with age (A), and with GFAP concentrations (B). Plasma NfL and GFAP were higher in the lean as compared to the obese individuals, and increased 6-months post bariatric surgery (C). Red circles: subjects with obesity; blue squares: lean subjects. Light pink: obese subject post bariatric surgery. GFAP glial fibrillary acidic protein, NfL Neurofilament light chain.

Figure 2

The correlation between NfL and GFAP with total eGFR was driven by the obese subjects. Red circles: subjects with obesity; blue squares: lean subjects.

Figure 3

6-months after bariatric surgery circulating NfL and GFAP levels were directly related to each other (A), and correlated inversely with total eGFR (B, C). GFAP glial fibrillary acidic protein, NfL neurofilament light chain, eGFR estimated glomerular filtration rate.

Figure 4

Plasma Neurofilament light chain correlated inversely with gray matter density in the whole dataset (A). This correlation was more widespread in the lean (B), compared to the obese (C) individuals. Statistical parametric mapping results (p < 0.05, false discovery rate (FDR) corrected; extent threshold k: 9937 (A), extent threshold k: 1120 (B); Extent threshold k: 7614 (C), X: 5, Y: − 10, Z: 9.5). Images were created using Mango (Multi-image Analysis GUI) software, version 4.1 (http://rii.uthscsa.edu/mango/).