Climate change accelerates the breakdown of plastics, increasing our exposure to microplastic-derived compounds, including bisphenols and phthalates, that act as xenoestrogens capable of disrupting hormonal and immune regulation. Separately, Epstein–Barr virus (EBV), which infects over 95% of adults worldwide and persists silently in immune cells, has been increasingly implicated in the development of both Alzheimer’s disease (AD) and multiple sclerosis (MS). In this preprint, we ask: could climate-amplified microplastic exposure intersect with EBV-related biology to shape vulnerability to these two diseases?

To address this, we developed a computational exposome modelling framework that integrates network toxicology and systems bioinformatics. By mapping the known and predicted human protein targets of six environmentally relevant microplastic compounds onto EBV–host protein interaction networks and disease-associated proteins for AD and MS, we identify molecular convergence points where environmental, viral, and disease-related pathways overlap. Despite the distinct pathologies of the two diseases, we identified a conserved set of 20 “dual-hit” host proteins simultaneously targeted by both EBV and microplastic compounds in both AD and MS networks.

Pathway enrichment analysis revealed that these convergence points are embedded in immune, oxidative stress, and endocrine signalling pathways, with important disease-specific differences. In MS, the dual-hit neighbourhood was dominated by innate and adaptive immune signalling, consistent with EBV’s established role in driving autoimmune demyelination. In AD, enrichment was stronger in neuronal, metabolic, and endocrine pathways, with estrogen signalling emerging as an AD-specific convergence point. Progesterone-mediated signalling was enriched in both diseases. These findings offer a biologically plausible molecular mechanism for the well-documented female-biased susceptibility to both conditions: microplastic-derived xenoestrogens may disrupt estrogen and progesterone homeostasis, weakening immune control over latent EBV and amplifying downstream neuroimmune dysregulation.

We propose a unifying exposome-based model in which climate-accelerated chemical exposures and persistent viral biology jointly reshape internal regulatory networks, not as isolated causes, but as converging amplifiers of neurological disease vulnerability. While experimental validation is required, this systems-level framework identifies specific molecular interfaces that can guide future mechanistic and therapeutic research.

To read the full article, visit: https://www.researchsquare.com/article/rs-8928857/v1