Multiple Transcriptomic Analyses Explore Potential Synaptic Biomarker Rabphilin-3A for Alzheimer's Disease

• Published in: Scientific reports 2024-08, Vol.14 (1), p.18717-16, Article 18717
• Main Authors: Nguyen, Doan Phuong Quy, Pham, Son, Jallow, Amadou Wurry, Ho, Nguyen-Tuong, Le, Bao, Quang, Hung Tran, Lin, Yi-Fang, Lin, Yung-Feng
• Format: Article
• Language: English
• Subjects: 631/378/1689; 692/53; 692/617; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Animal models; Animals; Biomarkers; Biomarkers - metabolism; Blood; Disease Models, Animal; DNA microarrays; Exocytosis; Gene expression; Gene Expression Profiling; Gene set enrichment analysis; Genes; Humanities and Social Sciences; Humans; Mice; Mice, Transgenic; Microarray; Molecular modelling; multidisciplinary; Neurodegenerative diseases; Neurons - metabolism; Older people; Population studies; Rabphilin-3A; Rabphilin-3A - genetics; Rabphilin-3A - metabolism; Science; Science (multidisciplinary); Sequence analysis; Signal transduction; Single-Cell Analysis - methods; Synapses - metabolism; Synaptic signaling; Therapeutic targets; Transcriptome; Transcriptomics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-66693-8

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder afflicting the elderly population worldwide. The identification of potential gene candidates for AD holds promises for diagnostic biomarkers and therapeutic targets. Employing a comprehensive strategy, this study integrated transcriptomic data from diverse data sources, including microarray and single-cell datasets from blood and tissue samples, enabling a detailed exploration of gene expression dynamics. Through this thorough investigation, 19 notable candidate genes were found with consistent expression changes across both blood and tissue datasets, suggesting their potential as biomarkers for AD. In addition, single cell sequencing analysis further highlighted their specific expression in excitatory and inhibitory neurons, the primary functional units in the brain, underscoring their relevance to AD pathology. Moreover, the functional enrichment analysis revealed that three of the candidate genes were downregulated in synaptic signaling pathway. Further validation experiments significantly showed reduced levels of rabphilin-3A (RPH3A) in 3xTg-AD model mice, implying its role in disease pathogenesis. Given its role in neurotransmitter exocytosis and synaptic function, further investigation into RPH3A and its interactions with neurotrophic proteins may provide valuable insights into the complex molecular mechanisms underlying synaptic dysfunction in AD.