Moyamoya disease: molecular signatures still need validation for diagnosis

Searching for markers in blood and cerebrospinal fluid

Moyamoya disease is a progressive cerebrovascular disorder: branches of the internal carotid arteries narrow or become blocked, leading to chronic ischemia and the formation of abnormal collateral vessels. Its mechanisms remain incompletely understood.

The review brings together studies analyzing proteins or metabolites in serum or cerebrospinal fluid. The researchers searched four bibliographic databases through April 13, 2026, and included 31 studies. Participants were mainly East Asian adults with bilateral disease.

The aim was to identify signatures that could complement digital subtraction angiography, described as the diagnostic gold standard, and shed light on prognosis or disease progression.

Recurring abnormalities, but no proof of causation

The findings highlight proteins involved in inflammatory signaling, blood vessel formation, and cytoskeletal remodeling. Metabolic analyses identify elevated branched-chain amino acids, disruptions to the urea cycle, and changes in lipid metabolism, among other findings.

These converging findings suggest several biological mechanisms to explore, including immune activation and endothelial dysfunction. However, they do not demonstrate that these abnormalities cause the disease or that correcting them would improve its course.

Clinical usefulness remains to be demonstrated

The available abstract provides no numerical diagnostic performance data that would allow the usefulness of a test to be assessed. It therefore does not support a conclusion that a molecular signature reliably distinguishes people with the disease, predicts their disease course, or can replace imaging.

Although the authors judged the methodological quality to be generally good, the studies often relied on small samples and a single center. Validation in larger, multicenter cohorts from diverse backgrounds remains necessary before any clinical use.

What we can take away

This review identifies consistent biological avenues for research in moyamoya disease. It validates neither a new diagnostic test nor a therapeutic target ready for use in practice.