Abstract 6135: Amyloid-β accumulation in glioblastoma is driven by vascular remodeling and APP-processing pathways

Abstract Background: Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis.Identifying biomarkers for targeted therapies remains a major challenge in GBM treatment.Recently, we demonstrated that amyloid-β (Aβ), a peptide classically associated with neurodegenerative diseases, accumulates in GBM tumors. This study aims to investigate the mechanism underlying Aβ accumulation in GBM tissues. Methods: Immunohistochemical analysis and confocal imaging were performed to assessAβ localization in human GBM tissue sections. Glial fibrillary acidic protein (GFAP), ionizedcalcium-binding adaptor molecule 1 (Iba1), and CD31 were used as markers of astrocytes, microglia, and blood vessels, respectively. Western blot analysis was performed toevaluate the expression of Aβ and amyloid precursor protein (APP), along with matrixmetalloproteinases 2 and 9 (MMP-2 and MMP-9), presenilin-1, nicastrin proteins involved inAβ production and vascular endothelial growth factor (VEGF). Pearson correlation analysis was conducted to assess relationships among Aβ, VEGF, MMP-2/9, presenilin-1, and nicastrin. Results: Confocal imaging revealed robust Aβ accumulation in blood vessels and in tumor regions with high vascularization, as well as strong Aβ accumulation in microglia and, to alesser extent, in glioma cells. Western blot analysis showed strong correlations betweenAβ levels and factors such as VEGF, MMP-2, and presenilin-1, indicating complex regulatory interactions driving Aβ accumulation. Conclusion: These findings demonstrate that Aβ accumulation in GBM is closely linked to tumor vascularization and microglial involvement. The strong correlations with VEGF, MMP-2, and presenilin-1 suggest that both vascular remodeling and proteolytic processing contribute to Aβ buildup.This study was supported by: NIH Grants 1R15CA287203 and 1R16GM153522 Citation Format: Felix Y. Narvaez Irizarry, Alondra M. Bermudez Adorno, Lilia Kucheryavykh. Amyloid-β accumulation in glioblastoma is driven by vascular remodeling and APP-processing pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6135.