Alterations in leucine metabolism, reflected by elevated leucine and reduced N-isovalerylglycine levels, are associated with MMD and contribute additional predictive value beyond conventional clinical factors.
Patients with moyamoya disease had higher serum leucine than healthy controls.
Patients with MMD had lower serum N-isovalerylglycine (N-IVA) levels than healthy controls.
Higher leucine was independently associated with greater odds of MMD after adjustment for clinical and laboratory variables.
Higher N-IVA was independently associated with lower odds of MMD.
Adding leucine to the baseline clinical model improved risk stratification.
Adding leucine, glycine, and N-IVA to the clinical model modestly increased discrimination and improved reclassification.
Serum leucine correlated positively with inflammatory and lipid-related indicators.
This study compared blood levels of leucine, an amino acid, and two related compounds (glycine and N-isovalerylglycine) in 337 people with moyamoya disease and 84 healthy controls. Moyamoya disease is a rare condition in which brain arteries narrow progressively. People with the disease had higher blood leucine and lower N-isovalerylglycine than healthy people, and these differences held up after accounting for other clinical and lab factors. When the researchers added these metabolite measurements to a model built from standard clinical factors, the model's ability to tell patients from controls improved only slightly (AUC 0.880 to 0.892), though it did better at reclassifying people into appropriate risk categories. Leucine levels were also linked to markers of inflammation and blood fats, suggesting a broader metabolic disturbance. This research suggests that leucine metabolism may be altered in moyamoya disease and could eventually help with risk assessment. However, the study compared patients and controls at one point in time, so it cannot show that leucine changes cause the disease. The associations were modest, and the authors say further mechanistic research is needed.
Fu M, Xu J, Zhang T, Luo Y, Wang L, Qi L, et al.. (2026). Association of leucine pathway metabolites with moyamoya disease and its clinical phenotypes.. Frontiers in neurology. https://doi.org/10.3389/fneur.2026.1875390