Is TGF-β1 a Biomarker of Huntington’s Disease Progression?

Klaudia Plinta,Nikola Zmarzły,Marcin Rudziński,Magdalena Wójcik-Pędziwiatr,Monika Rudzińska-Bar,Andrzej Plewka

doi:10.3390/jcm10133001

Abstract

Huntington’s disease (HD) is an autosomal dominant genetic disease that can be divided into preclinical and symptomatic stages. Due to the diverse HD phenotype, there is an urgent need to identify markers that would independently assess its severity. The aim of this study was to evaluate the use of plasma levels of TGF-β1 in the assessment of HD severity. One hundred HD patients and 40 healthy volunteers were included in the study. All HD patients underwent neurological and cognitive function assessment. TGF-β1 levels were determined in the plasma of all patients. The correlations between TGF-β1 levels and clinical profile and HD severity were also investigated. In symptomatic patients, cognitive decline was demonstrated, while in preclinical patients, no symptoms were found. Plasma levels of TGF-β1 in HD patients did not differ significantly from the control group and did not change with the progression of the disease. In addition, TGF-β1 levels also did not correlate with the severity of motor dysfunction. Positive correlations between plasma TGF-β1 concentration and intensity of cognitive impairment were found, but only in the early disease stage. There was no clear benefit in assessing plasma TGF-β1 levels in HD patients as a marker of disease severity.

Highlights

Huntington’s disease (HD) is a genetically determined, autosomal dominant neurodegenerative disease
Transforming growth factor β is a pleiotropic cytokine that exhibits a very wide range of functions in both physiological and pathological processes. It participates in the regulation of proliferation, apoptosis, and differentiation, as well as adhesion, which is possible due to canonical signaling with SMAD proteins and non-canonical signaling via phosphoinositide 3-kinase (PI3K), protein kinase B (PKB) and mitogen-activated protein kinases (MAPKs) [17]
We showed a relationship between plasma levels of TGF-β1 and described movement disorders, which may be helpful in the search for a marker of movement disorder severity

Summary

Introduction

Huntington’s disease (HD) is a genetically determined, autosomal dominant neurodegenerative disease. Incidence of HD worldwide is 2.71 per 100,000 people, ranging from 0.4 per 100,000 in Asian populations to 5.7 per 100,000 in North America, Europe and Australia [1]. Lower incidence has been noticed in the Far East countries, i.e., Japan, Taiwan and Hong Kong, with an average incidence of 1–7 patients per million population [1,2]. Early involvement of the motor cortex and the occipital lobe was reported, suggesting widespread brain pathology in HD. In MRI studies of HD patients, decreased striatal volume and white matter changes have been reported even in the preclinical phase of HD [3,4,5]

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