TGF-beta1 is associated with the progression of intracranial deep white matter lesions: a pilot study with 5 years of magnetic resonance imaging follow-up

Abstract

Objectives: Elevated expression of transforming growth factor (TGF)-beta1 has been reported in hereditary cerebral small-vessel (HCSV) disease. The aim of this study was to clarify whether TGF-beta1 is a risk factor for intracranial deep white matter lesions (DWLs) and their progression in a general elderly population.

Methods: The subjects included 81 participants (Groups DWL, DWLP, and C) who had voluntarily undergone a health examination and brain magnetic resonance imaging (MRI) in 2003 and 2008 and 43 age-matched patients with previous symptomatic brain infarctions. Deep white matter lesions were graded from Grade 0 to 3 according to the Fazekas classification. Group DWL (23 subjects) was defined as DWLs with no progression in the grade level, and Group DWLP (progression of DWL) (12 subjects) was defined as DWLs with an increase in one or more grade number and an apparent worsening of Grade 3.

Forty-six age-matched control subjects with consistent normal brain MRI were included in Group C. The associations between DWLs and various vascular risk factors, including peripheral blood TGF-beta1 levels, were examined.

Results: In addition to the classical risk factors, the highest TGF-beta1 levels were found in Group DWLP. The TGF-beta1 levels were significantly higher in Group DWLP than in Group DWL, and DWLP was significantly correlated with elevated TGF-beta1 levels (odds ratio [OR]  =  1·72).

Conclusions: The present data suggest that TGF-beta1 may be important in the pathogenesis and progression of DWLs, and it is expected to be useful as a clinical indicator reflecting the presence of intracranial white matter lesions.

Keywords:

• Deep white matter lesions (DWLs)
• Progression
• TGF-beta1

This work was partially supported by a Grant-in-Aid for Scientific Research (B) (No. 19390178) from the Ministry of Education, Science, Sports, and Culture of Japan.