Semaphorin 3G (SEMA3G) is a highly selective marker of cerebral amyloid angiopathy
- 1University of Sydney
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.
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BibTeX
@misc{balcomb2026semaphorin,
title = {{Semaphorin 3G (SEMA3G) is a highly selective marker of cerebral amyloid angiopathy}},
author = {K. Balcomb and J. Buchanan and A. Strobbe and D. Claus and A. Faustin and J. Schneider and T. Wisniewski and M. Sunde and E. Drummond},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750803},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750803v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Semaphorin 3G (SEMA3G) is a highly selective marker of cerebral amyloid angiopathy
AU - K. Balcomb
AU - J. Buchanan
AU - A. Strobbe
AU - D. Claus
AU - A. Faustin
AU - J. Schneider
AU - T. Wisniewski
AU - M. Sunde
AU - E. Drummond
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750803
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750803v1
AB - 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.
ER -