Brain MRS correlates with mitochondrial dysfunction biomarkers in MELAS-associated mtDNA mutations

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) and MELAS-Spectrum Syndrome (MSS) are debilitating mitochondrial DNA (mtDNA) diseases.
• Understanding the relationship between peripheral biochemical markers and brain changes is crucial for diagnosis and treatment.

Purpose of the Study:

• To investigate correlations between brain proton magnetic resonance spectroscopy (¹H-MRS) findings and serum biomarkers in patients with MELAS and MSS.
• To assess the relationship between brain metabolite concentrations and mtDNA heteroplasmy levels.

Main Methods:

• Recruited patients with MELAS and MSS, along with healthy controls.
• Measured serum lactate, alanine, and mtDNA heteroplasmy.
• Performed brain ¹H-MRS to analyze metabolite concentrations (NAA, Cho, mI) relative to creatine (Cr) in specific brain regions.

Main Results:

• Patients showed lower NAA/Cr ratios in the medial parieto-occipital cortex and cerebellum compared to controls.
• Reduced NAA/Cr ratios inversely correlated with serum lactate and muscle/blood mtDNA heteroplasmy.
• Ventricular lactate was present in most patients and correlated with serum lactate levels.

Conclusions:

• Established correlations between peripheral biochemical markers and in vivo brain markers of neurodegeneration in MELAS and MSS.
• These biomarkers can serve as signatures for disease progression and evaluating treatment efficacy.