Drug repurposing for Alzheimer's disease integrating transcriptome-wide association study and biological network...

Area of Science:

• Neuroscience
• Computational Biology
• Pharmacology

Background:

• Alzheimer's disease (AD) is characterized by protein deposits and molecular abnormalities.
• Current treatments for AD lack disease-modifying efficacy.

Purpose of the Study:

• To identify potential therapeutics for Alzheimer's disease using a network-based drug repurposing strategy.
• To target key proteins and biological pathways implicated in AD pathology.

Main Methods:

• Constructed a comprehensive biological network of AD-associated molecules and their regulatory interactions.
• Integrated data from GWAS, MRI-derived phenotypes, biomolecular interactions, and gene expression profiles.
• Utilized a computational approach for drug repurposing.

Main Results:

• Identified significant correlations between transcription factors with altered gene expression in AD patients.
• Prioritized drug candidates based on their mechanisms of action.
• Identified 43 drug candidates (28 FDA-approved, 15 experimental), including Baricitinib and Gabapentin, targeting AD pathology in brain regions like the cortex and hippocampus.

Conclusions:

• The study demonstrates a promising systematic drug repurposing strategy for identifying novel AD therapeutics.
• This approach combines network analysis and MRI-driven studies, offering potential for other neurological disorders.