Gene interactions analysis of brain spatial transcriptome for Alzheimer's disease

Area of Science:

• Neuroscience
• Genomics
• Molecular Biology

Background:

• Alzheimer's disease (AD) research increasingly uses spatial transcriptomics to map brain gene expression.
• Understanding gene interaction dynamics during amyloid-β (Aβ) accumulation in AD is crucial but remains limited.

Purpose of the Study:

• To investigate the spatial and temporal dynamics of gene interactions during Aβ accumulation in Alzheimer's disease.
• To identify key ligand-receptor pairs and transcription factors involved in AD pathogenesis.

Main Methods:

• Analysis of spatial transcriptomics datasets from AD mouse models and human brain data.
• Examination of ligand-receptor communication, transcription factor regulatory networks, and spot-specific networks.
• Validation using independent datasets and human single-nuclei RNA-seq data.

Main Results:

• Identified 17 ligand-receptor pairs exhibiting opposite trends during Aβ accumulation.
• Characterized specific ligand-receptor interactions within hippocampal layers across varying pathological stages.
• Discovered nerve function-related transcription factors and differentially associated genes in AD versus wild-type mice.

Conclusions:

• This study provides the first comprehensive analysis of spatio-temporal gene associations in Alzheimer's disease using spatial transcriptomics.
• Establishes a foundation for understanding AD etiology through the lens of complex, spatially dependent gene interactions.
• Highlights the potential of spatial transcriptomics for novel AD research perspectives.