Akademik Veri Yönetim Sistemi
7. ULUSLARARASI 36. ULUSAL BİYOFİZİK KONGRESi, Bursa, Türkiye, 3 - 06 Eylül 2025, ss.101-102, (Özet Bildiri)
Aim: Mitochondrial dysfunction plays a central role in the development of Alzheimer’s disease (AD); however, its association with amyloid beta accumulation remains unclear. This study investigates mitochondrial dynamics in peripheral blood mononuclear cells (PBMCs) and hippocampal tissue of 5xFAD transgenic mice, an established model of AD. Materials and Methods: Mitochondrial membrane potential, oxidative stress, and mitochondrial mass in PBMCs were assessed using flow cytometry. The expression levels of mitochondrial fusion (OPA1, MFN2) and fission (DRP1, phospho-DRP1 S616) proteins were measured by Western blotting at 3, 6, and 9 months of age. Ultrastructural mitochondrial morphology in hippocampal tissue was analyzed using transmission electron microscopy. Results: Significant alterations in mitochondrial dynamics were observed in transgenic (TG) mice compared to controls (CTR). Fission proteins (DRP1, phospho-DRP1 S616) were upregulated at 9 months, while fusion proteins (OPA1, MFN2) were downregulated in the hippocampus at 6 and 9 months. A similar reduction in MFN2 levels was noted in PBMCs at 9 months. Flow cytometry further revealed a marked decrease in mitochondrial membrane potential and mass, accompanied by increased mitochondrial superoxide production in PBMCs. Electron microscopy of the hippocampus showed abnormal mitochondrial morphology, including teardrop-shaped mitochondria, structural deformities, and disrupted mitochondria-ER contacts (MERCs). Notably, mitochondria-associated ER contact sites were more distantly spaced in TG mice. Additionally, dysregulation of key mitochondrial proteins such as VDAC, TOM20, and PINK1 was detected in both central and peripheral tissues. Conclusion: Our findings demonstrate that mitochondrial dysfunction occurs early in AD pathogenesis, affecting both the central nervous system and peripheral blood cells. This systemic impairment of mitochondrial dynamics may play a critical role in disease progression and represents a promising target for future therapeutic interventions in AD.