Odeta Bondarevaite

• BSc (Hons) Biochemistry
• Altered association of RAB39B with pathological protein aggregates in idiopathic neurodegenerative disease

Membrane trafficking, the movement of cellular components via vesicles, is one of many processes disrupted in neurodegenerative diseases, such as Alzheimer’s disease, Dementia with Lewy bodies and Parkinson’s disease. Previous genetic studies have associated a protein mediating this process, RAB39B, with intellectual disability and dementia pathology. However, the role of RAB39B in neurodegeneration has not yet been explained. This project investigated the presence of RAB39B in post-mortem human brain tissue affected by Alzheimer’s disease and Dementia with Lewy bodies, questioning its part in these pathologies. Using common neuropathological and biochemical laboratory techniques, we found that, in disease, RAB39B is recruited to the cellular membrane where it possesses its active form. This protein was also found to co-localise with amyloid plaques, a pathological hallmark of Alzheimer’s disease. The results of this project suggest that RAB39B may possess a defensive role against toxic cellular aggregates which might be suppressed in dementia. Further study of proteins such as RAB39B could improve our understanding of pathology in neurodegenerative disease and open opportunities for treatment development.

Funding source: Alzheimer’s Society

Project supervisor: Dr David Koss