Semaphorin 3G (SEMA3G) is a highly selective marker of cerebral amyloid angiopathy

Authors

Balcomb, K., Buchanan, J., Strobbe, A., Claus, D., Faustin, A., Schneider, J., Wisniewski, T., Sunde, M., Drummond, E.

Abstract

Biomarkers of cerebral amyloid angiopathy (CAA) are critically needed. We recently identified semaphorin 3G (SEMA3G) as a novel protein selectively enriched in CAA. Here, we aimed to determine if SEMA3G was a selective marker of CAA in a large cohort of human brain tissue spanning multiple neurodegenerative diseases and three brain regions, and to determine if SEMA3G directly interacts with amyloid beta (A{beta}). Multiplexed immunofluorescence showed that SEMA3G significantly accumulated only in CAA+ blood vessels in the brain in all cases. We also showed that SEMA3G preferentially associated with A{beta}40, A{beta}pS8 and A{beta}pE3, but not A{beta}42. Thioflavin T assays and transmission electron microscopy showed that SEMA3G directly interacted with A{beta} and slowed A{beta} aggregation in vitro, and that this effect was more pronounced for A{beta}40 than A{beta}42. Together our results demonstrate that SEMA3G is a highly specific marker of CAA in the brain.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 17 Sep 2026.

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