Genetic and Pathogenic Overlaps Between Autism Spectrum Disorder and Alzheimer's Disease: Evolutionary Features and Opportunities for Drug Repurposing.

Scientists studied genes linked to both autism and Alzheimer's disease, finding they share similar biological pathways called mTOR signaling. About half of autism-related genes connect to these pathways. The research suggests some existing medications and natural supplements that affect these pathways might potentially help with autism, though this needs further testing.

This computational study analyzed genetic networks linking autism spectrum disorder (ASD) and Alzheimer's disease (AD), focusing on mTOR signaling pathways. Researchers found that approximately half of ASD predisposition genes and two-fifths of AD predisposition genes connect to mTOR signaling. Phylostratigraphic analysis revealed both disorders involve evolutionarily ancient genes, with ASD genes showing signs of stabilizing selection. The study identified potential drug repurposing opportunities, suggesting existing medications and natural compounds that regulate mTOR pathways could be explored for ASD treatment, including propofol, dexamethasone, celecoxib, statins, and various natural compounds like berberine and resveratrol.

Identifies mTOR pathway as promising therapeutic target for ASD. Suggests potential for repurposing existing medications, though clinical trials needed to validate safety and efficacy. May inform personalized treatment approaches based on genetic profiles.

Computational study without clinical validation. No sample size reported. Drug repurposing suggestions based on pathway analysis rather than clinical trials. Unclear methodology for gene network reconstruction and compound selection.

Autism spectrum disorder (ASD) and Alzheimer's disease (AD) are neurodevelopmental and neurodegenerative disorders, respectively. While exome sequencing is routinely employed during the early stages of ASD diagnosis, it rarely influences therapeutic strategies. To address this gap, we have reconstructed and analyzed the gene networks linking autism spectrum disorders, Alzheimer's disease, and mTOR signaling. In addition, we have performed a phylostratigraphic analysis that reveals similarities and differences in the evolution of both ASD and Alzheimer's disease predisposition genes.

We have shown that almost half of the genes predisposing to autism and two-fifths of the genes predisposing to Alzheimer's disease are directly related to the mTOR signaling pathway. Analysis of Phylostratigraphic Age Index (PAI) value distributions revealed a significant enrichment of evolutionarily ancient genes in both ASD- and AD-related gene sets. When studying the distribution of ASD predisposition genes by Divergence Index (DI) values, a significant enrichment with genes having extremely low DI = 0 has been found. Such low DI values indicate that most likely these genes are under stabilizing selection.

Using the ANDVisio tool, both pharmacological and natural mTOR regulators with potential for ASD treatment were selected, such as propofol, dexamethasone, celecoxib, statins, berberine, resveratrol, quercetin, myricetin, mio-inositol, and several amino acids.