Alzheimer disease β-amyloid pathology accelerates age-related hearing loss: evidence from App ^NL-F “knock-in” mice

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.