Abstract WMP114: EZH2 Inhibitor Improves Cognitive Behavior in CAA

• DOI: 10.1161/str.55.suppl_1.wmp114
• Publication Date: 2024-02-01T10:11:28Z
• Authors: Zahid Iqbal; Ahmad El Hamamy; Ngoc Mai Le; Arya Ranjan; Li Qi; Chunfeng Tan; Louise D McCullough; Jun Li
• Keywords: Stroke

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-β (Aβ) in leptomeningeal and cortical vessels. CAA may lead to dementia stroke; however effective options currently are very limited treat or halt progression. EZH2 (enhancer zeste 2 polycomb repressive complex 2) a histone methyltransferase, key regulator inflammation microglia phagocytosis. The present study investigates therapeutic potential an inhibitor (GSK343) mice. Methods: Brain samples were collected from cohort 4 WT TgSwDI (CAA model) male mice lysed for immunoblot analysis quantify H3K27me3 expression levels. A second 10 20 (15 months old) randomly assigned into DMSO (vehicle) GSK343 groups. After performing baseline behavioral testing (Barnes maze NORT), TgSwDI-DMSO groups injected with 0.1% while TgSwDI-GSK343 (5 mg/kg) every other day intraperitoneally. 6 weeks treatment, was performed, brain tissues IHC. Data presented as Mean±SEM. Results: Immunoblot assays showed elevated comparison had improvements ability recognize novel object (58.36%±1.84) compared controls (45.04%±3.41) NORT ( p = 0.0006). latency escape (63.08±2.86) significantly faster GSK343-treated control (77.34±3.43) Barnes 0.003). IHC results line reduced Aβ hippocampus frontal cortex. Conclusions: Our revealed that upregulated CAA-model Pharmacological inhibition improved cognitive outcomes mice, suggesting possible target.