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Mapping molecular overlap of neurodegenerative diseases

Comparing the molecular pathophysiology of Alzheimer’s disease, ALS, and frontotemporal dementia with SemNet 2.0.

Artificial Intelligence-Assisted Comparative Analysis of the Overlapping Molecular Pathophysiology of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia

International Journal of Molecular Sciences · 25(24), 13450

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Study overview

  • Used SemNet 2.0 to compare amino-acid, peptide, and protein concepts associated with Alzheimer’s disease, ALS, and FTD in a knowledge graph derived from more than 33 million PubMed articles.
  • Ranked concepts with normalized HeteSim scores and visualized overlap with CompositeView. NLP and GPT-4o mapped the top-ranked 1% to eight biological processes, with three trained reviewers checking supporting evidence.

Key findings

  • FTD shared 99.9% of its retrieved molecular nodes with Alzheimer’s disease and/or ALS—a measure of literature-derived graph overlap, not patient-level disease equivalence.
  • Inflammation/immune response and synapse/neurotransmission each accounted for 19% of mapped intersections, followed by cell-cycle regulation at 15% and protein aggregation at 12%.
  • Publication and ontology biases can influence these associations. The proposed disease spectrum and regulatory explanations remain hypotheses requiring experimental or clinical validation.

Figures

Triangular CompositeView network of protein nodes shared across Alzheimer’s disease, ALS, and FTD
Figure 2 — CompositeView of the top 1% of amino-acid, peptide, and protein nodes across AD, ALS, and FTD.Source: Wei et al. (2024), Figure 2 · CC BY 4.0
Three Venn diagrams showing percentages of amino-acid, peptide, and protein nodes shared among Alzheimer’s disease, ALS, and FTD
Figure 1 — Molecular-node overlap, expressed as percentages relative to each disease. FTD’s retrieved nodes are almost entirely shared with AD and/or ALS.Source: Wei et al. (2024), Figure 1 · CC BY 4.0
Sunburst chart mapping high-ranking molecular nodes to eight biological processes and three pairwise disease intersections
Figure 3 — High-ranking intersecting molecular nodes mapped to biological processes. Segment widths represent node counts, with outer segments separating the disease pairs.Source: Wei et al. (2024), Figure 3 · CC BY 4.0
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