Abstract
Hearing is the largest modifiable mid-life risk factor for Alzheimer’s disease (AD), yet its link to dementia remains unclear. We identified a neurophysiological biomarker of AD risk using the non-invasive, rapidly acquired, and clinically translatable auditory brainstem response (ABR) in normal hearing knock-in rats (Swedish familial AD risk variant to Amyloid precursor protein, AppS; male and female). Human ABRs have been proposed as a biomarker for AD and related dementias. The novel metric reported here is derived from multidimensional parametric feature extraction on the distribution statistics of repeated single-trial ABR traces. We report accurate prediction of genetic risk for AD risk in young and aged rats: AppS separate clearly from healthy humanized (AppH) in sex- and age-dependent manners. Notably, auditory learning during young adulthood shifted the AppS ABR signature towards a healthy AppH-like state that maintained over time into older age. Altogether the findings support the utility of the ABR to track disease state, progression, and effects of intervention, and point to a central neural generator of auditory dysfunction related to AD risk. ABRs could provide a very early biomarker for detection of AD risk and used to test the synergy of auditory and cognitive functions in human dementia.
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Acknowledgements
We thank Dr. Marc Tambini and Dr. Luciano D’Adamio for their generous gifts of experimental animals and breeder knock-in rats, which supported the establishment of our colony and the completion of this work. We also thank all members of the CLEF Lab at Rutgers University, especially Nilay Ateşyakar, and Dr. Michal Beeri at the Herbert and Jacqueline Krieger Klein Alzheimer’s Research Center, for their continuous insight and valuable input into this project.
Funding
This work was supported by the National Institutes of Health, the National Institute on Deafness and Communication Disorders [R01-DC018561 to K.M.B.], as well as funding from the School of Arts & Sciences at Rutgers University—New Brunswick [to K.M.B.] and the Busch Biomedical Grant Program at Rutgers University [to K.M.B.]. E.B.T. was funded by the Nancy Lurie Marks Family Foundation Career Continuation Award.
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Aydin, A.G., Manoj, P., Ramadan, F. et al. Sound-evoked auditory neurophysiological signals are a window into prodromal functional differences in a preclinical model of Alzheimer’s disease. Sci Rep (2026). https://doi.org/10.1038/s41598-026-51854-8
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DOI: https://doi.org/10.1038/s41598-026-51854-8
