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High School Student with a Traditionally Underrepresented Background

HS Poster

Poster 49 - Deciphering RIN3's Role in Alzheimer’s Disease Pathogenesis: A Focus on Endocytic Dysregulation and Early Neurodegeneration

Saturday, October 26, 2024
10:00 AM - 12:00 PM EST
Location: Exhibit Hall E, F & G

Introduction: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder, primarily surfacing as memory loss and cognitive decline in elderly individuals. The RIN3 protein, which functions as a guanine nucleotide exchange factor (GEF), has been identified as a potential key player in neuronal signaling and endocytic trafficking, processes that are critical in the context of neurodegenerative diseases. RIN3 predominantly interacts with Rab proteins, with Rab5 being particularly important in regulating membrane trafficking and the processing of cellular materials. Recent research has highlighted RIN3 and the Rab family as catalysts for early stages of endocytosis. This can affect axonal transport impairment, neuronal atrophy, and enlarged early endosomes. This research aims to clarify RIN3’s underlying mechanisms that contribute to the development of early onset Alzheimer’s disease. By clarifying RIN3’s role in Alzhiemers pathogenesis, this research holds the potential to revolutionize early diagnosis, prevention, and treatment strategies.

Materials and

Methods: In this study, confocal microscopy was used to capture high-resolution images of stained mouse brain tissue sections, with a focus on cells surrounding the hippocampus. The neuronal nuclei were identified using NEUN, which was visualized through the confocal microscope. The primary protein of interest, RIN3, was isolated and analyzed to explore its role in endosomal signaling and trafficking pathways. The resulting images were then imported into Cellpose software for precise identification and quantitative assessment of cells in the hippocampal region. This approach facilitated a detailed investigation of RIN3's function in regulating endosomal processes, offering key insights into its potential involvement in Alzheimer's disease pathogenesis.

Results, Conclusions, and Discussions: Previous publishings have suggested a potential implication that RIN3 gene mutations increase risks for early onset Alzheimer’s Disease, but remains uncertain. In our study we found that the role of RIN3 affecting AD has been left inconclusive. Our research observed no significant differences in cell count, which are suspected to be associated with the condition of AD, between the different RIN3 genotypes (homozygous, heterozygous, and wildtype). Understanding this observation opens an investigation on further developing more accurate methods of analyzing cells. This includes the development of a machine learning model tasked to detect cells at a precise level. Doing so opens opportunities for a more comprehensive insight on genetic factors for Alzheimer’s Disease.
Our initial findings provide a foundation for future research. It is important to remember that Alzheimer’s is a multifactorial disease that is influenced by a combination of genetic and environmental factors. We hope to expand our data set with more annotated cell images to obtain a strong and more accurate model. Additionally, we plan to delve deeper into the specific roles of RIN3, GFAP, Neun, and Rad31 in Alzheimer's disease progression. Thus by examining the interplay of these makers and microglial cells, we aim to gain a more comprehensive understanding of the underlying mechanism of Alzheimers and hope to uncover new therapeutic targets and early intervention strategies that could significantly impact the future of Alzheimer’s research and treatment.

Acknowledgements (Optional): This work was supported by a generous gift from Beckman Laser Institute Inc. to LS. The high school students (*) participated in the UCSD IEM OPALS internship. Special thanks to Dr. Shu Chien from UCSD Bioengineering and Dr. Lizhu Chen from CorDx Inc. for their donations.

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