Research Paper Volume 8, Issue 3 pp 427—439

Expression of amyloid-β in mouse cochlear hair cells causes an early-onset auditory defect in high-frequency sound perception

Yasuhiro Omata 1, 4, , Suganya Tharasegaran 1, , Young-Mi Lim 1, , Yasutoyo Yamasaki 1, , Yasuhito Ishigaki 2, , Takanori Tatsuno 2, , Mitsuo Maruyama 3, , Leo Tsuda 1, ,

  • 1 Center for Development of Advanced Medicine for Dementia (CAMD), National Center for Geriatrics and Gerontology (NCGG), Obu, Aichi, Japan
  • 2 Division of Molecular and Cellular Biology, Kanazawa Medical University, Kanazawa, Ishikawa, Japan
  • 3 Department of Molecular Aging, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan
  • 4 Presend address: Department of Occupational and Environmental Health, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan

received: November 18, 2015 ; accepted: January 27, 2016 ; published: March 7, 2016 ;
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Increasing evidence indicates that defects in the sensory system are highly correlated with age-related neurodegenerative diseases, including Alzheimer's disease (AD). This raises the possibility that sensory cells possess some commonalities with neurons and may provide a tool for studying AD. The sensory system, especially the auditory system, has the advantage that depression in function over time can easily be measured with electrophysiological methods. To establish a new mouse AD model that takes advantage of this benefit, we produced transgenic mice expressing amyloid-β (Aβ), a causative element for AD, in their auditory hair cells. Electrophysiological assessment indicated that these mice had hearing impairment, specifically in high-frequency sound perception (>32 kHz), at 4 months after birth. Furthermore, loss of hair cells in the basal region of the cochlea, which is known to be associated with age-related hearing loss, appeared to be involved in this hearing defect. Interestingly, overexpression of human microtubule-associated protein tau, another factor in AD development, synergistically enhanced the Aβ-induced hearing defects. These results suggest that our new system reflects some, if not all, aspects of AD progression and, therefore, could complement the traditional AD mouse model to monitor Aβ-induced neuronal dysfunction quantitatively over time.


ABR: auditory brainstem response; AD: Alzheimer's disease; Aβ: amyloid-β; APP: amyloid precursor protein; ARHL: age-related hearing loss.