Home › Research › Risk factors
Alzheimer disease β-amyloid pathology accelerates age-related hearing loss: evidence from App NL-F “knock-in” mice
Fuentes-Santamaría V, Alvarado JC, Benitez Z, Gabaldón-Ull MC, Saido TC, Saito T, Lenarz T, Juiz JM.. bioRxiv, 2026-05-28
Topic: Disease mechanisms in lab and animal studies
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” App NL-F mouse reproduces β-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 App NL-F mouse. In adult C57BL/6J mice around seven-month-old, there were significant increases in auditory thresholds. In adult age-matched App NL-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 App NL-F relative to age-matched C57BL/6J mice, progressing from basal to apical cochlear turns. Spiral ganglion neuron loss also was larger. In adult App NL-F mice there was more atrophy and enlarged capillary lumen size in the stria vascularis (SV), supporting accelerated ARHL. These findings suggest that central β-amyloid pathology worsens age-related damage to the auditory receptor, thus accelerating ARHL. Damage to the SV and its capillaries in App NL-F mice point to exacerbation of strial and vascular pathology in the aging cochlea by central β-amyloid pathology. ARHL acceleration by central β-amyloid pathology may contribute to a vicious circle with implications for prevention and therapies. Highlights Age-related hearing loss worsens in a mouse model of Alzheimer β-amyloid pathology. Hearing thresholds further increase relative to naturally occurring hearing loss. Loss of outer hair cells and spiral ganglion neurons is larger. The stria vascularis and its microcirculation are more atrophic and damaged. Alzheimer disease may potentiate peripheral presbycusis.
Key findings
- We found evidence that the early-onset ARHL of the C57BL/6J mouse is accelerated in the App NL-F mouse.
- In adult C57BL/6J mice around seven-month-old, there were significant increases in auditory thresholds.
- In adult age-matched App NL-F mice, auditory thresholds were significantly more elevated, suggesting acceleration of ARHL.
- Outer hair cell loss was significantly increased in adult App NL-F relative to age-matched C57BL/6J mice, progressing from basal to apical cochlear turns.
- These findings suggest that central β-amyloid pathology worsens age-related damage to the auditory receptor, thus accelerating ARHL.
New to this subject? Start with our plain-English guide: Risk factors, ranked →
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mice”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Fuentes-Santamaría, V., Alvarado, J. C., Benitez, Z., Gabaldón-Ull, M. C., Saido, T. C., Saito, T., et al. (2026). Alzheimer disease β-amyloid pathology accelerates age-related hearing loss: evidence from App NL-F “knock-in” mice. bioRxiv. https://doi.org/10.64898/2026.05.25.727095
Vancouver
Fuentes-Santamaría V, Alvarado JC, Benitez Z, Gabaldón-Ull MC, Saido TC, Saito T, et al. Alzheimer disease β-amyloid pathology accelerates age-related hearing loss: evidence from App NL-F “knock-in” mice. bioRxiv. 2026. doi:10.64898/2026.05.25.727095.
BibTeX
@article{fuentessantamaria2026-b3cc5f32,
author = {Fuentes-Santamaría, V. and Alvarado, J. C. and Benitez, Z. and Gabaldón-Ull, M. C. and Saido, T. C. and Saito, T. and Lenarz, T. and Juiz, J. M.},
title = {{Alzheimer disease β-amyloid pathology accelerates age-related hearing loss: evidence from App NL-F “knock-in” mice}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.05.25.727095},
url = {https://doi.org/10.64898/2026.05.25.727095}
}
Related studies in Risk factors
Also tagged “hearing”
118 studies in the library carry the topic tag “hearing”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 118 tagged studies.