Hearing loss drives region-specific amyloid accumulation along the auditory pathway in female 5xFAD mice
- 1Department of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, MI 48109 USA
- 2Department of Cell and Developmental Biology, University of Michigan Medical School, Michigan, 48109 USA
Abstract
Hearing loss is a major modifiable risk factor for Alzheimer’s disease (AD), but how auditory deprivation engages specific neural circuits, particularly in a sex-dependent manner, to promote amyloid pathology remains unclear. We examined whether sound deprivation alters amyloid-beta (Aβ) deposition, auditory neural activity, and cognition in 5xFAD mice. Notably, sound deprivation using bilateral earplugging from 2 to 4 months selectively increased Aβ plaque burden in the inferior colliculus (IC) of female 5xFAD mice, with no comparable effect in males. This IC-selective pathology was accompanied by increased c-Fos expression in the IC. Microglial density was unchanged, but earplugging increased the fraction of plaque-associated microglia and reduced microglia–plaque distance specifically in the IC, suggesting local amplification of AD-related pathology at the plaque interface. 5xFAD mice without deprivation retained intact novel object recognition (NOR) at 6 months. In contrast, female 5xFAD mice with prior earplugging developed a selective NOR deficit despite no detectable increase in hippocampal plaque burden, whereas males remained unaffected. Together, these findings identify the IC as a female-vulnerable locus where transient sound deprivation drives persistent auditory-circuit hyperactivity, remodels microglia–plaque interactions, and accelerates region-specific amyloid pathology with extra-hippocampal cognitive consequences, highlighting sensory loss as modifiable risk factor in prodromal AD.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-64191-7.
Related
- Pathway‐specific polygenic risk scores modify the association between amyloid and tau PET accumulation in patients with Alzheimer's disease
- Auditory performance and cortical plasticity in blind individuals with sensorineural hearing loss: insights into dual sensory impairment
- Change in gut microbiome precedes symptomatic Alzheimer's disease and is correlated with amyloid-beta accumulation in the brain
- Carotid atherosclerotic burden and hearing function across auditory frequencies in a low-income rural Chinese population: a population-based cross-sectional study
- Neighborhood socioeconomic deprivation is associated with worse cognitive performance and in vivo amyloid accumulation.
BibTeX
@article{park2026hearing,
title = {{Hearing loss drives region-specific amyloid accumulation along the auditory pathway in female 5xFAD mice}},
author = {Jiwon Park and Se Yeon Jeong and Jun Hee Kim},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-64191-7},
url = {https://doi.org/10.1038/s41598-026-64191-7},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Hearing loss drives region-specific amyloid accumulation along the auditory pathway in female 5xFAD mice
AU - Jiwon Park
AU - Se Yeon Jeong
AU - Jun Hee Kim
PY - 2026
DA - 2026/07/29
JO - Scientific Reports
DO - 10.1038/s41598-026-64191-7
UR - https://doi.org/10.1038/s41598-026-64191-7
AB - Hearing loss is a major modifiable risk factor for Alzheimer’s disease (AD), but how auditory deprivation engages specific neural circuits, particularly in a sex-dependent manner, to promote amyloid pathology remains unclear. We examined whether sound deprivation alters amyloid-beta (Aβ) deposition, auditory neural activity, and cognition in 5xFAD mice. Notably, sound deprivation using bilateral earplugging from 2 to 4 months selectively increased Aβ plaque burden in the inferior colliculus (IC) of female 5xFAD mice, with no comparable effect in males. This IC-selective pathology was accompanied by increased c-Fos expression in the IC. Microglial density was unchanged, but earplugging increased the fraction of plaque-associated microglia and reduced microglia–plaque distance specifically in the IC, suggesting local amplification of AD-related pathology at the plaque interface. 5xFAD mice without deprivation retained intact novel object recognition (NOR) at 6 months. In contrast, female 5xFAD mice with prior earplugging developed a selective NOR deficit despite no detectable increase in hippocampal plaque burden, whereas males remained unaffected. Together, these findings identify the IC as a female-vulnerable locus where transient sound deprivation drives persistent auditory-circuit hyperactivity, remodels microglia–plaque interactions, and accelerates region-specific amyloid pathology with extra-hippocampal cognitive consequences, highlighting sensory loss as modifiable risk factor in prodromal AD. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-64191-7.
SN - 2045-2322
ER -