{
  "id": 7329431,
  "title": "Aβ42-Driven α-synuclein Fibril Polymorphism and Distinct Intracellular Aggregation",
  "url": "https://urgent.news/2026/09/14/a-42-driven-synuclein-fibril-polymorphism-and-distinct-intracellular",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-14T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750398v1?rss=1"
  },
  "original_language": "en",
  "account": "Aβ42 and α-synuclein aggregates often coexist in neurodegenerative diseases, but the molecular consequences of their interactions remain unclear. This study explored how distinct Aβ42 states—monomers and preformed fibrils (PFFs)—affect α-synuclein fibril formation, structure, and subsequent neuronal damage. Using Thioflavin T kinetics, the researchers found that Aβ42 monomers slowed α-synuclein fibril formation, whereas Aβ42 PFFs promoted accelerated aggregation, suggesting that the aggregation state of Aβ42 influences α-synuclein aggregation.\n\nFurther analyses using negative-stain TEM, proteinase K digestion, and solid-state NMR spectroscopy revealed that both Aβ42 monomers and PFFs altered α-synuclein fibril structures, leading to unique fibril conformations depending on Aβ42 concentration and aggregation state. To assess the impact of these structural variations on pathological activity, the team created α-synuclein PFF variants in the presence of varying amounts of Aβ42 monomers or PFFs and tested their effects on dopaminergic neuronal cells. The α-synuclein fibrils formed alongside Aβ42 PFFs demonstrated a higher potential to trigger intracellular α-synuclein aggregation compared to those formed with Aβ42 monomers. Conversely, fibrils formed with Aβ42 monomers showed seeding capacities similar to or less than those of α-synuclein PFFs.\n\nThese findings collectively illustrate that heterotypic interactions between Aβ42 and α-synuclein can reshape α-synuclein aggregation pathways and produce fibril conformations with distinct structural characteristics. Moreover, these variations in fibril structure correlate with differences in neuronal seeding activities. This study provides a molecular basis for understanding how cross-talk between amyloidogenic proteins may contribute to the structural and pathological heterogeneity observed in mixed neurodegenerative diseases.",
  "summary": "The frequent coexistence of -synuclein (-syn) and amyloid-{beta} (A{beta}) aggregates in neurodegenerative diseases suggests that heterotypic interactions between these amyloidogenic proteins may influence disease progression, yet their molecular consequences remain poorly understood. Here, we investigated how distinct aggregation states of A{beta}42, monomers and preformed fibrils (PFFs),…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}