{
  "id": 11225001,
  "title": "T1R2/T1R3 Identified as the Aβ Receptor: A New Mechanism Linking Aβ42/40 Ratio to Neuronal Hyperexcitability in Alzheimer's Disease",
  "url": "https://urgent.news/2026/10/01/t1r2-t1r3-identified-as-the-a-receptor-a-new-mechanism-linking-a-42",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-10-01T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754367v1?rss=1"
  },
  "original_language": "en",
  "account": "Alzheimer's disease (AD) is characterized by early neuronal hyperexcitability, which correlates with cognitive decline. A crucial diagnostic marker is the drop in soluble A{beta}42/40 ratio - from around 10% in cognitively normal individuals to approximately 5% in AD patients - that reliably forecasts progression to dementia. While commonly employed as a biomarker, the functional significance of this ratio has been unclear until now.\n\nIn a groundbreaking study, researchers determined that the reduced A{beta}42/40 ratio functions as an active ligand that triggers increased voltage-gated sodium current (INa). Contrary to the previously inert physiological ~10% ratio, the AD-associated 5% ratio activates INa, necessitating the presence of T1R2 and T1R3 receptors. Notably, T1R1 is not involved in this process. This receptor-specific detection mechanism has been demonstrated across various human cell lines expressing Nav1.1, Nav1.5, or Nav1.6 channels, as well as differentiated SH-SY5Y cells. Rodent NG108-15 cells, which are inherently insensitive, were rendered responsive upon expression of human T1R3, highlighting a human-specific detection mechanism.\n\nThese findings establish T1R2/T1R3 as the receptor that perceives the A{beta}42/40 ratio, bridging early A{beta} changes to neuronal hyperexcitability. Moreover, the human-specific nature of this pathway underscores the potential for developing humanized T1R2/T1R3 knock-in mice to validate this discovery in vivo, paving the way for potential therapeutic interventions aimed at restoring early neuronal function in AD patients.",
  "summary": "Early neuronal hyperexcitability is a hallmark of Alzheimer's disease (AD) and correlates with cognitive decline. A key diagnostic indicator is the reduction in soluble A{beta}42/40 ratio - from ~10% in cognitively normal individuals to ~5% in AD - which reliably predicts progression to dementia. Although widely used as a biomarker, whether this ratio plays an active signaling role has remained…",
  "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."
}