COCHLEAR DYSFUNCTION AS A NOVEL PERIPHERAL BIOMARKER OF ALZHEIMER’S DISEASE

Growing epidemiological evidence indicates a strong association between hearing loss and cognitive decline (PMID: 39096926; PMID: 35870677), suggesting that auditory dysfunction may represent an early and clinically relevant feature of neurodegenerative pathologies, such as Alzheimer’s disease (AD). However, while increasing attention has been devoted to the impact of hearing impairment on cognitive functions, whether dementia is associated with a specific susceptibility of the peripheral auditory system remains unexplored.
To this end, we investigated age-dependent cochlear alterations in a transgenic mouse model of AD (3×Tg-AD mice) compared to wild-type (WT) controls (B6129SF2/J mice). Functional, morphological, and molecular analyses were performed at 3, 6, 12, and 18 months of age to characterize the progression of cochlear degeneration and to assess the presence of key AD-related pathological markers within cochlear tissues.
Our results demonstrate an increased vulnerability of hair cells to aging processes in AD mice, with significantly higher cell death at 12 months of age compared to age-matched WT. Although auditory brainstem response (ABR) thresholds did not differ between strains, AD mice showed an early reduction in distortion product otoacoustic emissions (DPOAEs) from 6 months of age, indicating selective functional impairment of outer hair cells. We identified an age-dependent accumulation of AD-related pathological markers, including amyloid-β, phosphorylated Tau, and BACE1 in cochlear tissues, together with enhanced oxidative stress and inflammatory responses.
Collectively, these findings demonstrate functional, morphological, and molecular alterations in cochlear samples of AD mice, demonstrating that cochlear dysfunction can be an early peripheral biomarker of AD pathology.