title: Reduced acoustic startle response and peripheral hearing loss in the 5xFAD mouse model of Alzheimer's disease.
abstract: Hearing dysfunction has been associated with Alzheimer's disease (AD) in humans, but there is little data on the auditory function of mouse models of AD. Furthermore, characterization of hearing ability in mouse models is needed to ensure that tests of cognition that use auditory stimuli are not confounded by hearing dysfunction. Therefore, we assessed acoustic startle response and pre-pulse inhibition in the double transgenic 5xFAD mouse model of AD from 3-4 to 16 months of age. The 5xFAD mice showed an age-related decline in acoustic startle as early as 3-4 months of age. We subsequently tested auditory brainstem response (ABR) thresholds at 4 and 13-14 months of age using tone bursts at frequencies of 2-32 kHz. The 5xFAD mice showed increased ABR thresholds for tone bursts between 8 and 32 kHz at 13-14 months of age. Finally, cochleae were extracted and basilar membranes were dissected to count hair cell loss across the cochlea. The 5xFAD mice showed significantly greater loss of both inner and outer hair cells at the apical and basal ends of the basilar membrane than wild-type mice at 15-16 months of age. These results indicate that the 5xFAD mouse model of AD shows age-related decreases in acoustic startle responses, which are at least partially due to age-related peripheral hearing loss. Therefore, we caution against the use of cognitive tests that rely on audition in 5xFAD mice over 3-4 months of age, without first confirming that performance is not confounded by hearing dysfunction.
authors.affiliation: Department of Psychology & Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: T P
authors.initials: TP
authors.lastname: O'Leary
authors.affiliation: Department of Psychology & Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Shin
authors.affiliation: Department of Psychology & Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Fertan
authors.affiliation: Department of Psychology & Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: R N
authors.initials: RN
authors.lastname: Dingle
authors.affiliation: Department of Basic Medical Sciences, King Saud Bin Abdulaziz University for Health Science, Riyadh, Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Almuklass
authors.affiliation: Department of Psychology & Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: R K
authors.initials: RK
authors.lastname: Gunn
authors.affiliation: Department of School of Human Communication Disorders, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of School of Human Communication Disorders, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Psychology & Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: R E
authors.initials: RE
authors.lastname: Brown
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006198:Hair Cells, Auditory / Q000473:pathology; D034381:Hearing Loss / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013216:Reflex, Startle
chemical_list: D016564:Amyloid beta-Protein Precursor
keywords: 5xFAD; Alzheimer's disease; acoustic startle; age-related hearing loss; auditory brainstem response; behavior; hair cell; hearing; mice; pre-pulse inhibition