What they found
TL;DR (qwen3.6:35b): Alzheimer’s disease beta-amyloid pathology accelerates age-related hearing loss in mice, causing earlier and more severe outer hair cell and spiral ganglion neuron loss compared to controls. This suggests that central brain pathology exacerbates vascular and strial damage in the cochlea, potentially creating a vicious cycle between hearing loss and dementia.
Age-related hearing loss (ARHL) is a main acquired risk factor for dementia, including Alzheimer disease (AD), but links are unknown. We are using a mouse model with traits of both aging pathologies to test mechanistic interactions. The knock-in AppNL-F mouse reproduces beta-amyloid pathology in brain regions homologous to those involved in human AD. Because it was generated from the C57BL/6J mouse, it expresses early signs of ARHL, previously reported in this inbred strain. We found evidence that the early-onset ARHL of the C57BL/6J mouse is accelerated in the AppNL-F mouse. In adult C57BL/6J mice around seven-month-old, there were significant increases in auditory thresholds. In adult age-matched AppNL-F mice, auditory thresholds were significantly more elevated, suggesting acceleration of ARHL. In old mice, past thirteen months of age, hearing thresholds were equally elevated in both strains. Outer hair cell loss was significantly increased in adult AppNL-F relative to age-matched C57BL/6J mice, progressing from basal to apical cochlear turns. Spiral ganglion neuron loss also was larger. In adult AppNL-F mice there was more atrophy and enlarged capillary lumen size in the stria vascularis (SV), supporting accelerated ARHL. These findings suggest that central beta-amyloid pathology worsens age-related damage to the auditory receptor, thus accelerating ARHL. Damage to the SV and its capillaries in AppNL-F mice point to exacerbation of strial and vascular pathology in the aging cochlea by central beta-amyloid pathology. ARHL acceleration by central beta-amyloid pathology may contribute to a vicious circle with implications for prevention and therapies.
How this applies to our program
This study highlights the critical role of cochlear vasculature and the stria vascularis in hearing loss, which is relevant to STRC/DFNB16 research as these structures support the metabolic demands of hair cells. Understanding how systemic or central pathologies accelerate hair cell death may reveal shared mechanisms or therapeutic targets for preventing hearing loss in genetic and age-related contexts.
Key numbers
- Significant increases in auditory thresholds observed in adult C57BL/6J mice around seven months of age
- Hearing thresholds became equally elevated in both strains in mice past thirteen months of age
- Outer hair cell loss was significantly increased in adult AppNL-F mice relative to age-matched controls
Links
- biorxiv_id: https://www.biorxiv.org/content/10.64898/2026.05.25.727095
- DOI: https://doi.org/10.64898/2026.05.25.727095
Connections
[source]auto-indexed 2026-05-29 by strc-lit-watch