Soluble Klotho and Brain Atrophy in Alcoholism

Alcohol Alcohol. 2018 Sep 1;53(5):503-510. doi: 10.1093/alcalc/agy037.

Abstract

Aim: Fibroblast growth factor (FGF-23) and α-Klotho (Klotho) levels may be altered in inflammatory conditions, possibly as compensatory mechanisms. Klotho exerts a protective effect on neurodegeneration and improves learning and cognition. No data exist about the association of Klotho and FGF-23 levels with brain atrophy observed in alcoholics. The aim of this study is to explore these relationships.

Short summary: FGF-23 and Klotho levels are altered in inflammation, possibly as compensatory mechanisms. Klotho enhances learning, but its role in ethanol-mediated brain atrophy is unknown. We found higher FGF-23 and lower Klotho levels in 131 alcoholics compared with 41 controls. Among cirrhotics, Klotho was higher and inversely related to brain atrophy.

Methods: The study was performed on 131 alcoholic patients (54 cirrhotics) and 41 age- and sex-matched controls, in whom a brain computed tomography (CT) was performed and several indices were calculated.

Results: Marked brain atrophy was observed among patients when compared with controls. Patients also showed higher FGF-23 and lower Klotho values. However, among cirrhotics, Klotho values were higher. Klotho was inversely related to brain atrophy (for instance, ventricular index (ρ = -0.23, P = 0.008)), especially in cirrhotics. Klotho was also directly related to tumor necrosis factor (TNF) alpha (ρ = 0.22; P = 0.026) and inversely to transforming growth factor (TGF)-β (ρ = -0.34; P = 0.002), but not to C-reactive protein (CRP) or malondialdehyde levels. FGF-23 was also higher among cirrhotics but showed no association with CT indices.

Conclusions: Klotho showed higher values among cirrhotics, and was inversely related to brain atrophy. FGF-23, although high among patients, especially cirrhotics, did not show any association with brain atrophy. Some inflammatory markers or cytokines, such as CRP or TGF-β were related to brain atrophy.

MeSH terms

  • Aged
  • Alcoholism / blood*
  • Alcoholism / diagnostic imaging*
  • Atrophy
  • Biomarkers / blood
  • Brain / diagnostic imaging
  • Brain Diseases / blood*
  • Brain Diseases / diagnostic imaging*
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Glucuronidase / blood*
  • Humans
  • Klotho Proteins
  • Male
  • Middle Aged

Substances

  • Biomarkers
  • FGF23 protein, human
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Glucuronidase
  • Klotho Proteins